BACKGROUND: In the United States, ongoing efforts to increase individual- and population-level physical activity have made little to no progress over the past decade in reducing the percentage of individuals who report no leisure-time physical activity. The purpose of the current study is to further assess the relationship between social vulnerability and the prevalence of physical inactivity at the county level. METHODS: We merged county-level data on physical inactivity prevalence, the Social Vulnerability Index (SVI), and the American Nations regional cultures schematic. RESULTS: Physical inactivity significantly correlated (P < .001) with the overall SVI score and all subtheme scores to varying levels of strength. Clear and statistically significant heterogeneity in the SVI scores was apparent across distinct regions using the American Nations model, consistent with previously demonstrated patterns of physical inactivity prevalence. CONCLUSIONS: On a national level, physical inactivity prevalence is unacceptably high and has not appreciably improved over the past decade. Within the United States, high levels of social vulnerability and physical inactivity are concentrated within specific geographic regions that need tailored solutions to resolve health disparities.