Recent advances in the fossil record, anatomy, and evolutionary history of South American turtles allow a thorough analysis of their changes in diversity, and to identify several major extinction events. With the onset of the breakup of Pangea in the Middle Jurassic, turtles begin to diversify, giving rise to the main South American turtle clades some of which survive until present. The first peak of diversity was achieved in the Early Cretaceous. A first extinction event is recognized at the end of the Early Cretaceous, affecting mainly the pelomedusoids in northern latitudes and coinciding with the final separation of South America from Africa. The K–Pg boundary mass extinction affected deeply the thriving turtles in South America by reducing their diversity in half. Reduction of diversity continued on the aftermath of the K–Pg extinction, roughly until the middle Eocene and the final isolation of South America from Antarctica. In this “new” continent, the diversity of the surviving turtles continued to decrease, until an injection of biodiversity from Africa, with the arrival of tortoises, which helped to recover the diversity levels. The Andean uplift in Late Oligocene–Early Miocene and the associated climate and habitat changes posed new problems for the turtles of the continent. New injections of biodiversity took place at the end of the Neogene with the Great American Biotic Interchange, as novel clades reached South America from the North. The modern biodiversity of South American turtles took its final shape only during the last million years.