Horn sharks (Elasmobranchii: Heterodontus Blainville) correspond to a genus of chondrichthyan fishes, mostly distributed in warm-temperate to tropical regions of the Pacific and Indian Oceans. The fossil record shows that, in contrast to its current distribution, horn sharks were widely distributed both in the eastern Pacific and western Atlantic during the Neogene, being subsequently extirpated from some of these areas. In this contribution, we describe new Heterodontus teeth from three Pliocene localities in the Coquimbo Region, in north-central Chile, and make an extensive revision of the fossil record of the genus in the Americas, in order to specify the timing of their extirpation in the southeastern Pacific and discuss the possible causes of this event. The new specimens described herein belong to a species with a Heterodontus francisci type dentition. Our analysis suggest that the removal of horn sharks occurred in the context of a general faunal turnover in the transition from Pliocene to Pleistocene, and that it was probably controlled by an interplay between the oceanographic, tectono-eustatic and ecological changes occurred in the region at that time.