<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with Wdesk from Workiva-->
<!--Copyright 2023 Workiva-->
<!--r:912e1565-2dff-44dd-bfb3-af6c8a11fb3c,g:26ec8c83-18eb-4378-8ac1-2975735259ca-->
<xs:schema xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:prax="http://praxismedicines.com/20221231" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:dtr-types="http://www.xbrl.org/dtr/type/2020-01-21" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" attributeFormDefault="unqualified" elementFormDefault="qualified" targetNamespace="http://praxismedicines.com/20221231">
  <xs:import namespace="http://fasb.org/srt/2022" schemaLocation="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd"/>
  <xs:import namespace="http://fasb.org/us-gaap/2022" schemaLocation="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd"/>
  <xs:import namespace="http://www.w3.org/1999/xlink" schemaLocation="http://www.xbrl.org/2003/xlink-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/2003/instance" schemaLocation="http://www.xbrl.org/2003/xbrl-instance-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/2003/linkbase" schemaLocation="http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/dtr/type/2020-01-21" schemaLocation="https://www.xbrl.org/dtr/type/2020-01-21/types.xsd"/>
  <xs:import namespace="http://xbrl.org/2005/xbrldt" schemaLocation="http://www.xbrl.org/2005/xbrldt-2005.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/dei/2022" schemaLocation="https://xbrl.sec.gov/dei/2022/dei-2022.xsd"/>
  <xs:annotation>
    <xs:appinfo>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="prax-20221231_lab.xml" xlink:role="http://www.xbrl.org/2003/role/labelLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="prax-20221231_pre.xml" xlink:role="http://www.xbrl.org/2003/role/presentationLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="prax-20221231_cal.xml" xlink:role="http://www.xbrl.org/2003/role/calculationLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="prax-20221231_def.xml" xlink:role="http://www.xbrl.org/2003/role/definitionLinkbaseRef" xlink:type="simple"/>
      <link:roleType id="CoverPage" roleURI="http://praxismedicines.com/role/CoverPage">
        <link:definition>0000001 - Document - Cover Page</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AuditInformation" roleURI="http://praxismedicines.com/role/AuditInformation">
        <link:definition>0000002 - Document - Audit Information</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="ConsolidatedBalanceSheets" roleURI="http://praxismedicines.com/role/ConsolidatedBalanceSheets">
        <link:definition>0000003 - Statement - Consolidated Balance Sheets</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="ConsolidatedBalanceSheetsParenthetical" roleURI="http://praxismedicines.com/role/ConsolidatedBalanceSheetsParenthetical">
        <link:definition>0000004 - Statement - Consolidated Balance Sheets (Parenthetical)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="ConsolidatedStatementsofOperations" roleURI="http://praxismedicines.com/role/ConsolidatedStatementsofOperations">
        <link:definition>0000005 - Statement - Consolidated Statements of Operations</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="ConsolidatedStatementsofComprehensiveLoss" roleURI="http://praxismedicines.com/role/ConsolidatedStatementsofComprehensiveLoss">
        <link:definition>0000006 - Statement - Consolidated Statements of Comprehensive Loss</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="ConsolidatedStatementsofStockholdersEquity" roleURI="http://praxismedicines.com/role/ConsolidatedStatementsofStockholdersEquity">
        <link:definition>0000007 - Statement - Consolidated Statements of Stockholders' Equity</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="ConsolidatedStatementsofStockholdersEquityParenthetical" roleURI="http://praxismedicines.com/role/ConsolidatedStatementsofStockholdersEquityParenthetical">
        <link:definition>0000008 - Statement - Consolidated Statements of Stockholders' Equity (Parenthetical)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="ConsolidatedStatementsofCashFlows" roleURI="http://praxismedicines.com/role/ConsolidatedStatementsofCashFlows">
        <link:definition>0000009 - Statement - Consolidated Statements of Cash Flows</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NatureoftheBusiness" roleURI="http://praxismedicines.com/role/NatureoftheBusiness">
        <link:definition>0000010 - Disclosure - Nature of the Business</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPolicies" roleURI="http://praxismedicines.com/role/SummaryofSignificantAccountingPolicies">
        <link:definition>0000011 - Disclosure - Summary of Significant Accounting Policies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="RestrictedCash" roleURI="http://praxismedicines.com/role/RestrictedCash">
        <link:definition>0000012 - Disclosure - Restricted Cash</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="MarketableSecurities" roleURI="http://praxismedicines.com/role/MarketableSecurities">
        <link:definition>0000013 - Disclosure - Marketable Securities</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueofFinancialAssets" roleURI="http://praxismedicines.com/role/FairValueofFinancialAssets">
        <link:definition>0000014 - Disclosure - Fair Value of Financial Assets</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="PropertyandEquipmentNet" roleURI="http://praxismedicines.com/role/PropertyandEquipmentNet">
        <link:definition>0000015 - Disclosure - Property and Equipment, Net</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AccruedExpenses" roleURI="http://praxismedicines.com/role/AccruedExpenses">
        <link:definition>0000016 - Disclosure - Accrued Expenses</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingencies" roleURI="http://praxismedicines.com/role/CommitmentsandContingencies">
        <link:definition>0000017 - Disclosure - Commitments and Contingencies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="UCBOptionandLicenseAgreement" roleURI="http://praxismedicines.com/role/UCBOptionandLicenseAgreement">
        <link:definition>0000018 - Disclosure - UCB Option and License Agreement</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommonStockandPreferredStock" roleURI="http://praxismedicines.com/role/CommonStockandPreferredStock">
        <link:definition>0000019 - Disclosure - Common Stock and Preferred Stock</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedCompensation" roleURI="http://praxismedicines.com/role/StockBasedCompensation">
        <link:definition>0000020 - Disclosure - Stock-Based Compensation</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SignificantAgreements" roleURI="http://praxismedicines.com/role/SignificantAgreements">
        <link:definition>0000021 - Disclosure - Significant Agreements</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NetLossperShare" roleURI="http://praxismedicines.com/role/NetLossperShare">
        <link:definition>0000022 - Disclosure - Net Loss per Share</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IncomeTaxes" roleURI="http://praxismedicines.com/role/IncomeTaxes">
        <link:definition>0000023 - Disclosure - Income Taxes</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="RelatedPartyTransactions" roleURI="http://praxismedicines.com/role/RelatedPartyTransactions">
        <link:definition>0000024 - Disclosure - Related Party Transactions</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="EmployeeBenefitPlan" roleURI="http://praxismedicines.com/role/EmployeeBenefitPlan">
        <link:definition>0000025 - Disclosure - Employee Benefit Plan</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="Restructuring" roleURI="http://praxismedicines.com/role/Restructuring">
        <link:definition>0000026 - Disclosure - Restructuring</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SubsequentEvents" roleURI="http://praxismedicines.com/role/SubsequentEvents">
        <link:definition>0000027 - Disclosure - Subsequent Events</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesPolicies" roleURI="http://praxismedicines.com/role/SummaryofSignificantAccountingPoliciesPolicies">
        <link:definition>0000028 - Disclosure - Summary of Significant Accounting Policies (Policies)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesTables" roleURI="http://praxismedicines.com/role/SummaryofSignificantAccountingPoliciesTables">
        <link:definition>0000029 - Disclosure - Summary of Significant Accounting Policies (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="MarketableSecuritiesTables" roleURI="http://praxismedicines.com/role/MarketableSecuritiesTables">
        <link:definition>0000030 - Disclosure - Marketable Securities (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueofFinancialAssetsTables" roleURI="http://praxismedicines.com/role/FairValueofFinancialAssetsTables">
        <link:definition>0000031 - Disclosure - Fair Value of Financial Assets (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="PropertyandEquipmentNetTables" roleURI="http://praxismedicines.com/role/PropertyandEquipmentNetTables">
        <link:definition>0000032 - Disclosure - Property and Equipment, Net (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AccruedExpensesTables" roleURI="http://praxismedicines.com/role/AccruedExpensesTables">
        <link:definition>0000033 - Disclosure - Accrued Expenses (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentandContingenciesTables" roleURI="http://praxismedicines.com/role/CommitmentandContingenciesTables">
        <link:definition>0000034 - Disclosure - Commitment and Contingencies (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommonStockandPreferredStockTables" roleURI="http://praxismedicines.com/role/CommonStockandPreferredStockTables">
        <link:definition>0000035 - Disclosure - Common Stock and Preferred Stock (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedCompensationTables" roleURI="http://praxismedicines.com/role/StockBasedCompensationTables">
        <link:definition>0000036 - Disclosure - Stock-Based Compensation (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NetLossperShareTables" roleURI="http://praxismedicines.com/role/NetLossperShareTables">
        <link:definition>0000037 - Disclosure - Net Loss per Share (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IncomeTaxesTables" roleURI="http://praxismedicines.com/role/IncomeTaxesTables">
        <link:definition>0000038 - Disclosure - Income Taxes (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="OrganizationConsolidationandPresentationofFinancialStatementsDetails" roleURI="http://praxismedicines.com/role/OrganizationConsolidationandPresentationofFinancialStatementsDetails">
        <link:definition>0000039 - Disclosure - Organization, Consolidation and Presentation of Financial Statements (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesAdditionalInformationDetails" roleURI="http://praxismedicines.com/role/SummaryofSignificantAccountingPoliciesAdditionalInformationDetails">
        <link:definition>0000040 - Disclosure - Summary of Significant Accounting Policies - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesSummaryofCashCashEquivalentsandRestrictedCashDetails" roleURI="http://praxismedicines.com/role/SummaryofSignificantAccountingPoliciesSummaryofCashCashEquivalentsandRestrictedCashDetails">
        <link:definition>0000041 - Disclosure - Summary of Significant Accounting Policies - Summary of Cash, Cash Equivalents and Restricted Cash (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesPropertyandEquipmentEstimatedUsefulLifeDetails" roleURI="http://praxismedicines.com/role/SummaryofSignificantAccountingPoliciesPropertyandEquipmentEstimatedUsefulLifeDetails">
        <link:definition>0000042 - Disclosure - Summary of Significant Accounting Policies - Property and Equipment Estimated Useful Life (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="RestrictedCashDetails" roleURI="http://praxismedicines.com/role/RestrictedCashDetails">
        <link:definition>0000043 - Disclosure - Restricted Cash (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="MarketableSecuritiesInvestmentProfileDetails" roleURI="http://praxismedicines.com/role/MarketableSecuritiesInvestmentProfileDetails">
        <link:definition>0000044 - Disclosure - Marketable Securities - Investment Profile (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="MarketableSecuritiesInvestmentProfileDetails_1" roleURI="http://praxismedicines.com/role/MarketableSecuritiesInvestmentProfileDetails_1">
        <link:definition>0000044 - Disclosure - Marketable Securities - Investment Profile (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="MarketableSecuritiesAdditionalInformationDetails" roleURI="http://praxismedicines.com/role/MarketableSecuritiesAdditionalInformationDetails">
        <link:definition>0000045 - Disclosure - Marketable Securities - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueofFinancialAssetsSummaryofFinancialAssetsMeasuredatFairValueonaRecurringBasisDetails" roleURI="http://praxismedicines.com/role/FairValueofFinancialAssetsSummaryofFinancialAssetsMeasuredatFairValueonaRecurringBasisDetails">
        <link:definition>0000046 - Disclosure - Fair Value of Financial Assets - Summary of Financial Assets Measured at Fair Value on a Recurring Basis (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="PropertyandEquipmentNetDetails" roleURI="http://praxismedicines.com/role/PropertyandEquipmentNetDetails">
        <link:definition>0000047 - Disclosure - Property and Equipment, Net (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AccruedExpensesSummaryofAccruedExpensesDetails" roleURI="http://praxismedicines.com/role/AccruedExpensesSummaryofAccruedExpensesDetails">
        <link:definition>0000048 - Disclosure - Accrued Expenses - Summary of Accrued Expenses (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingenciesAdditionalInformationDetails" roleURI="http://praxismedicines.com/role/CommitmentsandContingenciesAdditionalInformationDetails">
        <link:definition>0000049 - Disclosure - Commitments and Contingencies - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingenciesOperatingLeaseConsolidatedBalanceSheetDetails" roleURI="http://praxismedicines.com/role/CommitmentsandContingenciesOperatingLeaseConsolidatedBalanceSheetDetails">
        <link:definition>0000050 - Disclosure - Commitments and Contingencies - Operating Lease, Consolidated Balance Sheet (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingenciesTotalLeaseCostsDetails" roleURI="http://praxismedicines.com/role/CommitmentsandContingenciesTotalLeaseCostsDetails">
        <link:definition>0000051 - Disclosure - Commitments and Contingencies - Total Lease Costs (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingenciesFutureLeasePaymentsDetails" roleURI="http://praxismedicines.com/role/CommitmentsandContingenciesFutureLeasePaymentsDetails">
        <link:definition>0000052 - Disclosure - Commitments and Contingencies - Future Lease Payments (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingenciesFutureLeasePaymentsDetails_1" roleURI="http://praxismedicines.com/role/CommitmentsandContingenciesFutureLeasePaymentsDetails_1">
        <link:definition>0000052 - Disclosure - Commitments and Contingencies - Future Lease Payments (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingenciesWeightedAverageRemainingLeaseTermandWeightedAverageIncrementalBorrowingRateDetails" roleURI="http://praxismedicines.com/role/CommitmentsandContingenciesWeightedAverageRemainingLeaseTermandWeightedAverageIncrementalBorrowingRateDetails">
        <link:definition>0000053 - Disclosure - Commitments and Contingencies - Weighted Average Remaining Lease Term and Weighted Average Incremental Borrowing Rate (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="UCBOptionandLicenseAgreementDetails" roleURI="http://praxismedicines.com/role/UCBOptionandLicenseAgreementDetails">
        <link:definition>0000054 - Disclosure - UCB Option and License Agreement (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommonStockandPreferredStockAdditionalInformationDetails" roleURI="http://praxismedicines.com/role/CommonStockandPreferredStockAdditionalInformationDetails">
        <link:definition>0000055 - Disclosure - Common Stock and Preferred Stock - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommonStockandPreferredStockSummaryofCommonStockReservedForFutureIssuanceDetails" roleURI="http://praxismedicines.com/role/CommonStockandPreferredStockSummaryofCommonStockReservedForFutureIssuanceDetails">
        <link:definition>0000056 - Disclosure - Common Stock and Preferred Stock - Summary of Common Stock Reserved For Future Issuance (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedCompensationAdditionalInformationDetails" roleURI="http://praxismedicines.com/role/StockBasedCompensationAdditionalInformationDetails">
        <link:definition>0000057 - Disclosure - Stock-Based Compensation - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedCompensationSummaryofRestrictedStockActivityDetails" roleURI="http://praxismedicines.com/role/StockBasedCompensationSummaryofRestrictedStockActivityDetails">
        <link:definition>0000058 - Disclosure - Stock-Based Compensation - Summary of Restricted Stock Activity (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedCompensationSummaryofStockOptionActivityDetails" roleURI="http://praxismedicines.com/role/StockBasedCompensationSummaryofStockOptionActivityDetails">
        <link:definition>0000059 - Disclosure - Stock-Based Compensation - Summary of Stock Option Activity (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedCompensationScheduleofFairValueofStockOptionAwardsontheGrantDateUsingtheBlackScholesOptionValuationModelDetails" roleURI="http://praxismedicines.com/role/StockBasedCompensationScheduleofFairValueofStockOptionAwardsontheGrantDateUsingtheBlackScholesOptionValuationModelDetails">
        <link:definition>0000060 - Disclosure - Stock-Based Compensation - Schedule of Fair Value of Stock Option Awards on the Grant Date Using the Black-Scholes Option Valuation Model (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="StockBasedCompensationSummaryofStockBasedCompensationExpenseDetails" roleURI="http://praxismedicines.com/role/StockBasedCompensationSummaryofStockBasedCompensationExpenseDetails">
        <link:definition>0000061 - Disclosure - Stock-Based Compensation - Summary of Stock-Based Compensation Expense (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SignificantAgreementsDetails" roleURI="http://praxismedicines.com/role/SignificantAgreementsDetails">
        <link:definition>0000062 - Disclosure - Significant Agreements (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NetLossperShareSummaryofantidilutivesecuritiesexcludedfromcomputationofearningspershareDetails" roleURI="http://praxismedicines.com/role/NetLossperShareSummaryofantidilutivesecuritiesexcludedfromcomputationofearningspershareDetails">
        <link:definition>0000063 - Disclosure - Net Loss per Share - Summary of antidilutive securities excluded from computation of earnings per share (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IncomeTaxesScheduleofEffectiveIncomeTaxRateReconciliationDetails" roleURI="http://praxismedicines.com/role/IncomeTaxesScheduleofEffectiveIncomeTaxRateReconciliationDetails">
        <link:definition>0000064 - Disclosure - Income Taxes - Schedule of Effective Income Tax Rate Reconciliation (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IncomeTaxesNetDeferredTaxAssetsDetails" roleURI="http://praxismedicines.com/role/IncomeTaxesNetDeferredTaxAssetsDetails">
        <link:definition>0000065 - Disclosure - Income Taxes - Net Deferred Tax Assets (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IncomeTaxesAdditionalInformationDetails" roleURI="http://praxismedicines.com/role/IncomeTaxesAdditionalInformationDetails">
        <link:definition>0000066 - Disclosure - Income Taxes - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="EmployeeBenefitPlanDetails" roleURI="http://praxismedicines.com/role/EmployeeBenefitPlanDetails">
        <link:definition>0000067 - Disclosure - Employee Benefit Plan (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="RestructuringDetails" roleURI="http://praxismedicines.com/role/RestructuringDetails">
        <link:definition>0000068 - Disclosure - Restructuring (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SubsequentEventsDetails" roleURI="http://praxismedicines.com/role/SubsequentEventsDetails">
        <link:definition>0000069 - Disclosure - Subsequent Events (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
    </xs:appinfo>
  </xs:annotation>
  <xs:element id="prax_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsIssuedInPeriod" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsIssuedInPeriod" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="prax_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainNoncurrentBeforeTax" abstract="false" name="DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainNoncurrentBeforeTax" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="prax_TwentyTwentyEmployeeStockIncentivePlanMember" abstract="true" name="TwentyTwentyEmployeeStockIncentivePlanMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="prax_AccruedPersonnelRelatedExpensesCurrent" abstract="false" name="AccruedPersonnelRelatedExpensesCurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="prax_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossCurrentBeforeTax" abstract="false" name="DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossCurrentBeforeTax" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="prax_UCBMember" abstract="true" name="UCBMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="prax_OfficeFurnitureAndEquipmentMember" abstract="true" name="OfficeFurnitureAndEquipmentMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="prax_IonisMember" abstract="true" name="IonisMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="prax_SaleOfStockConsiderationReceivedGrossAmount" abstract="false" name="SaleOfStockConsiderationReceivedGrossAmount" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="prax_IncreaseDecreaseInOperatingLeaseLiabilities" abstract="false" name="IncreaseDecreaseInOperatingLeaseLiabilities" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="prax_A2022OfferingsMember" abstract="true" name="A2022OfferingsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="prax_ScheduleOfCommonStockReservedForFutureIssuanceTable" abstract="true" name="ScheduleOfCommonStockReservedForFutureIssuanceTable" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:hypercubeItem" type="xbrli:stringItemType"/>
  <xs:element id="prax_ProceedsFromAtTheMarketOfferingsNetOfIssuanceCosts" abstract="false" name="ProceedsFromAtTheMarketOfferingsNetOfIssuanceCosts" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="prax_TwoThousandTwentyEmployeeStockIncentivePlanMember" abstract="true" name="TwoThousandTwentyEmployeeStockIncentivePlanMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="prax_RogconMember" abstract="true" name="RogconMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="prax_UnvestedRestrictedStockUnitsMember" abstract="true" name="UnvestedRestrictedStockUnitsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="prax_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsIssuedInPeriodWeightedAverageGrantDateFairValue" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsIssuedInPeriodWeightedAverageGrantDateFairValue" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:perShareItemType"/>
  <xs:element id="prax_ScheduleOfCommonStockReservedForFutureIssuanceTableTextBlock" abstract="false" name="ScheduleOfCommonStockReservedForFutureIssuanceTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <xs:element id="prax_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossNoncurrentBeforeTax" abstract="false" name="DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossNoncurrentBeforeTax" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="prax_SignificantAgreementsTextBlock" abstract="false" name="SignificantAgreementsTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <xs:element id="prax_RevenueRemainingPerformanceObligationVariableConsiderationAmount" abstract="false" name="RevenueRemainingPerformanceObligationVariableConsiderationAmount" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="prax_TwoThousandTwentyEmployeeStockPurchasePlanMember" abstract="true" name="TwoThousandTwentyEmployeeStockPurchasePlanMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="prax_TwentySeventeenEmployeeStockIncentivePlanMember" abstract="true" name="TwentySeventeenEmployeeStockIncentivePlanMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="prax_LaboratoryEquipmentMember" abstract="true" name="LaboratoryEquipmentMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="prax_PercentageIncreaseInAnnualBaseRent" abstract="false" name="PercentageIncreaseInAnnualBaseRent" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="prax_LicensingAgreementsProfitSharePaymentsMember" abstract="true" name="LicensingAgreementsProfitSharePaymentsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="prax_AssetsAndLiabilitiesLesseeTableTextBlock" abstract="false" name="AssetsAndLiabilitiesLesseeTableTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <xs:element id="prax_DeferredOfferingCostsIncludedInAccountsPayableAndAccruedExpenses" abstract="false" name="DeferredOfferingCostsIncludedInAccountsPayableAndAccruedExpenses" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="prax_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainCurrentBeforeTax" abstract="false" name="DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainCurrentBeforeTax" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="prax_LettersOfCreditReceivableNoncurrent" abstract="false" name="LettersOfCreditReceivableNoncurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="prax_AuditInformationAbstract" abstract="true" name="AuditInformationAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="prax_DeferredTaxAssetsTaxDeferredExpenseAmortization" abstract="false" name="DeferredTaxAssetsTaxDeferredExpenseAmortization" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="prax_LettersOfCreditReceivableCurrent" abstract="false" name="LettersOfCreditReceivableCurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="prax_FollowOnPublicOfferingMember" abstract="true" name="FollowOnPublicOfferingMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="prax_DeferredTaxLiabilitiesOperatingLeaseRightOfUseAsset" abstract="false" name="DeferredTaxLiabilitiesOperatingLeaseRightOfUseAsset" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="prax_JefferiesOpenMarketAgreementMember" abstract="true" name="JefferiesOpenMarketAgreementMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="prax_TwentyTwentyEmployeeStockPurchasePlanMember" abstract="true" name="TwentyTwentyEmployeeStockPurchasePlanMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="prax_ScheduleOfCommonStockReservedForFutureIssuanceLineItems" abstract="true" name="ScheduleOfCommonStockReservedForFutureIssuanceLineItems" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="prax_AccruedExternalResearchAndDevelopmentExpensesCurrent" abstract="false" name="AccruedExternalResearchAndDevelopmentExpensesCurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="prax_DeferredTaxAssetsOperatingLeaseRightOfUseAsset" abstract="false" name="DeferredTaxAssetsOperatingLeaseRightOfUseAsset" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
</xs:schema>
