Biological communities in Mexico experienced profound changes in species composition and structure as a consequence of the environmental fluctuations during the Pleistocene. Based on the recent and fossil Mexican mammal checklists, we determine the distribution, composition, diversity, and community structure of late Pleistocene mammalian faunas, and analyze extinction patterns and response of individual species to environmental changes. We conclude that (1) differential extinctions occurred at family, genus, and species level, with a major impact on species heavier than 100 kg, including the extinction all proboscideans and several ruminants; (2) Pleistocene mammal communities in Mexico were more diverse than recent ones; and (3) the current assemblages of species are relatively young. Furthermore, Pleistocene relicts support the presence of biogeographic corridors; important refugia existed as well as centers of speciation in isolated regions. We identified seven corridors: eastern USA–Sierra Madre Oriental corridor, Rocky Mountains–Sierra Madre Occidental corridor, Central United States–Northern Mexico corridor, Transvolcanic Belt–Sierra Madre del Sur corridor, western USA–Baja California corridor, Tamaulipas–Central America gulf lowlands corridor, and Sonora–Central America Pacific lowlands corridor. Our study suggests that present mammalian assemblages are very different than the ones in the late Pleistocene.