Mass extinctions have repeatedly shaped global biodiversity. The Cretaceous-Paleogene (K-Pg) mass extinction caused the demise of numerous vertebrate groups, and its aftermath saw the rapid diversification of surviving mammals, birds, frogs, and teleost fishes. However, the effects of the K-Pg extinction on the evolution of snakes—a major clade of predators comprising over 3,700 living species—remains poorly understood. Here, we combine an extensive molecular dataset with phylogenetically and stratigraphically constrained fossil calibrations to infer an evolutionary timescale for Serpentes. We reveal a potential diversification among crown snakes associated with the K-Pg mass extinction, led by the successful colonization of Asia by the major extant clade Afrophidia. Vertebral morphometrics suggests increasing morphological specialization among marine snakes through the Paleogene. The dispersal patterns of snakes following the K-Pg underscore the importance of this mass extinction event in shaping Earth’s extant vertebrate faunas.