Assessing the effects of early nonpharmaceutical interventions on coronavirus disease 2019 (COVID-19) spread is crucial for understanding and planning future control measures to combat the pandemic. We use observations of reported infections and deaths, human mobility data, and a metapopulation transmission model to quantify changes in disease transmission rates in U.S. counties from 15 March to 3 May 2020. We find that marked, asynchronous reductions of the basic reproductive number occurred throughout the United States in association with social distancing and other control measures. Counterfactual simulations indicate that, had these same measures been implemented 1 to 2 weeks earlier, substantial cases and deaths could have been averted and that delayed responses to future increased incidence will facilitate a stronger rebound of infections and death. Our findings underscore the importance of early intervention and aggressive control in combatting the COVID-19 pandemic.