Abundant, readily identifiable, and biostratigraphically resolved specimens make mosasaurs ideal candidates to test fluxes in generic richness and morphological trends among marine vertebrates during the late Cretaceous. More than 1800 globally distributed mosasaur specimens are allocated to fifteen substage-level stratigraphically correlated assemblages. These data are quantitatively analyzed to illuminate trends within the group. Following their first appearance in the Cenomanian, mosasaurs experienced a significant radiation in the Coniacian and Santonian. Richness levels continued increasing into the Maastrichtian while mosasaurs incrementally exploited new predatory niches recognized via accumulation of novel dental morphologies. Their extinction at the end of the Cretaceous occurred at the zenith of mosasaur morphological and ecological diversity.