Cardiovascular disease (CVD) is the leading cause of death in the United States, but CVD mortality rates vary substantially across U.S. counties. Recent explanations about geographic disparities in CVD mortality focus mainly on differences in demographic composition, socioeconomic conditions, health care access, and health behaviors. It is unclear what role air pollution plays in explaining geographic disparities in CVD mortality. In this study, I examine the associations between air pollution and county-level CVD mortality for the years 2016 to 2018 and how these associations vary across rural and urban counties. To answer these questions, I merge county-level data from multiple sources and apply spatial models. I find that higher concentrations of fine particulate matter (PM 2.5) are associated with higher CVD mortality rates, net of important county-level confounders such as socioeconomic and racial/ethnic composition. Moreover, PM 2.5 concentration is more strongly associated with CVD mortality in rural than in urban areas. These findings reveal the importance of air quality for reducing the CVD burden in the United States. Reducing PM 2.5 concentration could not only reduce geographic disparities in CVD deaths but could also reduce the rural mortality penalty.