Abstract Background Weeks after issuing social distancing orders to suppress severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and reduce growth in cases of severe coronavirus disease 2019 (COVID-19), all US states and the District of Columbia partially or fully relaxed these measures. Methods We identified all statewide social distancing measures that were implemented and/or relaxed in the United States between 10 March and 15 July 2020, triangulating data from state government and third-party sources. Using segmented linear regression, we estimated the extent to which relaxation of social distancing affected epidemic control, as indicated by the time-varying, state-specific effective reproduction number (Rt). Results In the 8 weeks prior to relaxation, mean Rt declined by 0.012 units per day (95% confidence interval [CI], −.013 to −.012), and 46/51 jurisdictions achieved Rt < 1.0 by the date of relaxation. After relaxation of social distancing, Rt reversed course and began increasing by 0.007 units per day (95% CI, .006–.007), reaching a mean Rt of 1.16. Eight weeks later, the mean Rt was 1.16 and only 9/51 jurisdictions were maintaining an Rt < 1.0. Parallel models showed similar reversals in the growth of COVID-19 cases and deaths. Indicators often used to motivate relaxation at the time of relaxation (eg, test positivity rate <5%) predicted greater postrelaxation epidemic growth. Conclusions We detected an immediate and significant reversal in SARS-CoV-2 epidemic suppression after relaxation of social distancing measures across the United States. Premature relaxation of social distancing measures undermined the country’s ability to control the disease burden associated with COVID-19.