SARS-CoV-2, the virus that causes COVID-19, is constantly mutating, leading to new variants (1). Variants have the potential to affect transmission, disease severity, diagnostics, therapeutics, and natural and vaccine-induced immunity. In November 2020, CDC established national surveillance for SARS-CoV-2 variants using genomic sequencing. As of May 6, 2021, sequences from 177,044 SARS-CoV-2-positive specimens collected during December 20, 2020-May 6, 2021, from 55 U.S. jurisdictions had been generated by or reported to CDC. These included 3,275 sequences for the 2-week period ending January 2, 2021, compared with 25,000 sequences for the 2-week period ending April 24, 2021 (0.1% and 3.1% of reported positive SARS-CoV-2 tests, respectively). Because sequences might be generated by multiple laboratories and sequence availability varies both geographically and over time, CDC developed statistical weighting and variance estimation methods to generate population-based estimates of the proportions of identified variants among SARS-CoV-2 infections circulating nationwide and in each of the 10 U.S. Department of Health and Human Services (HHS) geographic regions.* During the 2-week period ending April 24, 2021, the B.1.1.7 and P.1 variants represented an estimated 66.0% and 5.0% of U.S. SARS-CoV-2 infections, respectively, demonstrating the rise to predominance of the B.1.1.7 variant of concern† (VOC) and emergence of the P.1 VOC in the United States. Using SARS-CoV-2 genomic surveillance methods to analyze surveillance data produces timely population-based estimates of the proportions of variants circulating nationally and regionally. Surveillance findings demonstrate the potential for new variants to emerge and become predominant, and the importance of robust genomic surveillance. Along with efforts to characterize the clinical and public health impact of SARS-CoV-2 variants, surveillance can help guide interventions to control the COVID-19 pandemic in the United States.