Abstract Objective To examine regional variation in physical distancing trends over the course of the COVID-19 pandemic, and to investigate inequalities within regions by race and socioeconomic status (SES). Methods Race and SES information from the American Community Survey were matched with location data from mobile device location pings at the Census block group level. We present trends in the proportion of residents staying at home by Census region, race, and SES from February-August, 2020. Results From March-August, the stay-at-home proportion was highest in the Northeast (0.23-0.31) and lowest in the South (0.22-0.28). Nationally, the stay-at-home proportion was higher in block groups with a higher percentage of Blacks, likely because Blacks disproportionately live in urban areas, where stay-at-home rates are higher. Physical distancing was higher among block groups that are wealthier, more educated, or contain the lowest proportion of frontline workers. Conclusions Disparities in physical distancing behaviors exist across U.S. regions, with a pronounced Southern and rural disadvantage. Results from this study can be used to guide planning and policy recommendations related to COVID-19 mitigation.