From January 21 through February 23, 2020, a total of 14 cases of coronavirus disease 2019 (COVID-19) were diagnosed in six U.S. states, including 12 cases in travelers arriving from China and two in household contacts of persons with confirmed infections. An additional 39 cases were identified in persons repatriated from affected areas outside the United States (1). Starting in late February, reports of cases with no recent travel to affected areas or links to known cases signaled the initiation of pandemic spread in the United States (2). By mid-March, transmission of SARS-CoV-2, the virus that causes COVID-19, had accelerated, with rapidly increasing case counts indicating established transmission in the United States. Ongoing traveler importation of SARS-CoV-2, attendance at professional and social events, introduction into facilities or settings prone to amplification, and challenges in virus detection all contributed to rapid acceleration of transmission during March. Public health responses included intensive efforts to detect cases and trace contacts, and implementation of multiple community mitigation strategies. Because most of the population remains susceptible to infection, recognition of factors associated with amplified spread during the early acceleration period will help inform future decisions as locations in the United States scale back some components of mitigation and strengthen systems to detect a potential transmission resurgence. U.S. circulation of SARS-CoV-2 continues, and sustained efforts will be needed to prevent future spread within the United States.