<?xml version="1.0" encoding="US-ASCII"?>
<!-- DFIN New ActiveDisclosure (SM) XBRL Linkbase Document - http://www.dfinsolutions.com/ -->
<!-- Creation Date :2023-05-23T06:00:05.4547+00:00 -->
<!-- Copyright (c) 2023 Donnelly Financial Solutions, Inc. All Rights Reserved. -->
<link:linkbase xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all" xlink:type="simple"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default" xlink:type="simple"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain" xlink:type="simple"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member" xlink:type="simple"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension" xlink:type="simple"/>
  <link:roleRef roleURI="http://ir.achievelifesciences.com/20230523/taxonomy/role/Role_DocumentDocumentAndEntityInformation" xlink:href="achv-20230523.xsd#Role_DocumentDocumentAndEntityInformation" xlink:type="simple"/>
  <link:definitionLink xlink:type="extended" xlink:role="http://ir.achievelifesciences.com/20230523/taxonomy/role/Role_DocumentDocumentAndEntityInformation">
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentInformationLineItems" xlink:label="dei_DocumentInformationLineItems"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentInformationTable" xlink:label="dei_DocumentInformationTable"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressesAddressTypeAxis" xlink:label="dei_EntityAddressesAddressTypeAxis"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_AddressTypeDomain" xlink:label="dei_AddressTypeDomain"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_AddressTypeDomain" xlink:label="dei_AddressTypeDomain_default"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_OtherAddressMember" xlink:label="dei_OtherAddressMember"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentType" xlink:label="dei_DocumentType"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_AmendmentFlag" xlink:label="dei_AmendmentFlag"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_DocumentPeriodEndDate" xlink:label="dei_DocumentPeriodEndDate"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityRegistrantName" xlink:label="dei_EntityRegistrantName"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityCentralIndexKey" xlink:label="dei_EntityCentralIndexKey"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityEmergingGrowthCompany" xlink:label="dei_EntityEmergingGrowthCompany"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityFileNumber" xlink:label="dei_EntityFileNumber"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityIncorporationStateCountryCode" xlink:label="dei_EntityIncorporationStateCountryCode"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityTaxIdentificationNumber" xlink:label="dei_EntityTaxIdentificationNumber"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressAddressLine1" xlink:label="dei_EntityAddressAddressLine1"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressAddressLine2" xlink:label="dei_EntityAddressAddressLine2"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressCityOrTown" xlink:label="dei_EntityAddressCityOrTown"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressStateOrProvince" xlink:label="dei_EntityAddressStateOrProvince"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressCountry" xlink:label="dei_EntityAddressCountry"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_EntityAddressPostalZipCode" xlink:label="dei_EntityAddressPostalZipCode"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_CityAreaCode" xlink:label="dei_CityAreaCode"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_LocalPhoneNumber" xlink:label="dei_LocalPhoneNumber"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_WrittenCommunications" xlink:label="dei_WrittenCommunications"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_SolicitingMaterial" xlink:label="dei_SolicitingMaterial"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_PreCommencementTenderOffer" xlink:label="dei_PreCommencementTenderOffer"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_PreCommencementIssuerTenderOffer" xlink:label="dei_PreCommencementIssuerTenderOffer"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_Security12bTitle" xlink:label="dei_Security12bTitle"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_TradingSymbol" xlink:label="dei_TradingSymbol"/>
    <link:loc xlink:type="locator" xlink:href="https://xbrl.sec.gov/dei/2022/dei-2022.xsd#dei_SecurityExchangeName" xlink:label="dei_SecurityExchangeName"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_DocumentInformationTable" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="dei_EntityAddressesAddressTypeAxis" xlink:to="dei_AddressTypeDomain" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="dei_EntityAddressesAddressTypeAxis" xlink:to="dei_AddressTypeDomain_default" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_AddressTypeDomain" xlink:to="dei_OtherAddressMember" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_DocumentType" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="0" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="dei_DocumentInformationTable" xlink:to="dei_EntityAddressesAddressTypeAxis" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="1" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_AmendmentFlag" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="2" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_DocumentPeriodEndDate" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="3" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityRegistrantName" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="4" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityCentralIndexKey" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="5" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityEmergingGrowthCompany" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="6" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityFileNumber" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="7" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityIncorporationStateCountryCode" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="8" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityTaxIdentificationNumber" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="9" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityAddressAddressLine1" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="10" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityAddressAddressLine2" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="11" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityAddressCityOrTown" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="12" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityAddressStateOrProvince" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="13" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityAddressCountry" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="14" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_EntityAddressPostalZipCode" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="15" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_CityAreaCode" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="16" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_LocalPhoneNumber" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="17" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_WrittenCommunications" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="18" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_SolicitingMaterial" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="19" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_PreCommencementTenderOffer" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="20" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_PreCommencementIssuerTenderOffer" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="21" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_Security12bTitle" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="22" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_TradingSymbol" priority="2" use="optional"/>
    <link:definitionArc xlink:type="arc" order="23" xbrldt:closed="false" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="dei_DocumentInformationLineItems" xlink:to="dei_SecurityExchangeName" priority="2" use="optional"/>
  </link:definitionLink>
</link:linkbase>
