Implementing social distancing, business closures, and other non-pharmaceutical interventions (NPIs) in the U.S. two weeks sooner, during the earliest stages of the COVID-19 pandemic, may have prevented more than a million cases and saved more than 59,000 lives prior to May 3, 2020, when many state and local governments began relaxing restrictions, according to a new metapopulation modeling study. The results highlight the importance of quick and aggressive NPI implementation to counter transmission of the SARS-CoV-2 virus and could help inform efforts to control new surges in the U.S. and elsewhere in the world. Seeking to understand the impact of timing when implementing NPIs, Sen Pei and colleagues first built a metapopulation model of COVID-19 transmission in all 3,142 U.S. counties during the period spanning February 21 through May 3, 2020. They built the model using county-level data of confirmed cases and deaths compiled by and commuter mobility data from the U.S. Census, adjusting the latter for reductions in mobility due to NPIs implemented beginning around March 15. The model revealed notable yet asynchronous reductions in disease transmission rates, reflected in changes to the estimated effective basic reproduction number (Re) in most counties during this time period. They then performed counterfactual simulations with the same model, moving the timing of NPI implementation either one week or two weeks sooner. In the first model, advancing NPIs by a week, to March 8, resulted in 601,667 fewer confirmed cases and 32,335 fewer deaths nationwide as of May 3. In the second model, implementing NPIs a full two weeks earlier, on March 1, resulted in 1,041,261 fewer confirmed cases and 59,351 fewer deaths. Pei et al. acknowledge that their modeling simplifies some assumptions related to general uncertainty, economic concerns, administrative decision-making, and public adherence to social distancing rules. However, they also point to continuing successes in countries such as South Korea, New Zealand, Vietnam, and Iceland that did implement NPIs in early March, suggesting that tens of thousands of cases and deaths in the U.S. “could have been averted, not merely postponed.”