Even though Neogene outcrops along the temperate Pacific coast of South America harbor a rich marine vertebrate fossil record, no studies have examined the diversification patterns of these taxa. Here, we analyze diversification trends based on the stratigraphic ranges of 86 genera of marine vertebrates, including sharks, rays, chimaeras, marine mammals, and seabirds. The richness of genera shows a hump-shaped trend, with maximum values around the late Miocene, driven by a large pulse of origination during mid-Miocene and higher extinction rates during the Pliocene. Trends varied markedly among taxa and departed largely from expectations based on global diversification patterns. Moreover, these trends cannot be explained solely as a sampling artifact derived from sampling intensity (i.e., number of occurrences) or sedimentary rock availably (i.e., number of geologic maps). A large fraction of genera (42%) went globally extinct by the late Pliocene–Pleistocene, and the extinction was highly selective according to different ecological and life-history traits. An analysis using “randomForest” showed that taxonomic structure and the geographic midpoint of distribution could explain up to 83% of extinction of genera. The extinction was taxonomically clumped (i.e., disproportionally high in Cetacea and very low in Carcharhiniformes) and concentrated in the northern area of the temperate Pacific coast of South America. Our results suggest that the particular paleogeographic, paleoclimatic, and paleoceanographic events that took place during the Neogene along the temperate Pacific coast of South America had a significant effect on the structure of marine biodiversity.