<p>Epidemiologic research has found worsening behavioral health in the USA since 2020. Local policies may have contributed to these patterns and associated disparities. However, scant research has systematically documented county-level COVID-19-era policymaking or empirically investigated its health impacts. To investigate this question, we linked the US COVID-19 County Policy Database—a novel database with weekly data from 2020 to 2021 on 26 policies for 309 primarily urban counties—to data on adult behavioral health from the cross-sectional 2021 National Survey on Drug Use and Health (<i>N</i> = 25,600). We created measures of policy comprehensiveness by aggregating individual policies into an overall score, and into three domains: containment/closure, economic response, and public health. Outcomes included any past-30-day use and frequency of use of multiple substances (alcohol, binge alcohol, cigarettes, marijuana, non-marijuana illicit drug use, and vaping) and past-30-day psychological distress. Models adjusted for individual covariates, county fixed effects, and time-varying county-level COVID-19 covariates. We found that increases in overall policy comprehensiveness—and comprehensiveness in each of three domains—over time were not associated with the behavioral health outcomes assessed. Meanwhile, stratified models found some variability in associations across sex, racial/ethnic, education, and urban subgroups. This study established the feasibility, utility, and potential challenges of linking newly available COVID-19-related county policy data with health data to examine county-level policy influences on behavioral health. Further research is needed to inform responses to current behavioral health needs and future public health emergencies.</p>