CDC continues to track the evolution of SARS-CoV-2, including the Omicron variant and its descendants, using national genomic surveillance. This report summarizes U.S. trends in variant proportion estimates during May 2023-September 2024, a period when SARS-CoV-2 lineages primarily comprised descendants of Omicron variants XBB and JN.1. During summer and fall 2023, multiple descendants of XBB with immune escape substitutions emerged and reached >10% prevalence, including EG.5-like lineages by June 24, FL.1.5.1-like lineages by August 5, HV.1 lineage by September 30, and HK.3-like lineages by November 11. In winter 2023, the JN.1 variant emerged in the United States and rapidly attained predominance nationwide, representing a substantial genetic shift (>30 spike protein amino acid differences) from XBB lineages. Descendants of JN.1 subsequently circulated and reached >10% prevalence, including KQ.1-like and KP.2-like lineages by April 13, KP.3 and LB.1-like lineages by May 25, and KP.3.1.1 by July 20. Surges in COVID-19 cases occurred in winter 2024 during the shift to JN.1 predominance, as well as in summer 2023 and 2024 during circulation of multiple XBB and JN.1 descendants, respectively. The ongoing evolution of the Omicron variant highlights the importance of continued genomic surveillance to guide medical countermeasure development, including the selection of antigens for updated COVID-19 vaccines.