The Pleistocene and modern mammal faunas of southern North America strongly differ in taxonomic makeup, distribution, and physiognomy. The former faunal complexes are part of the ancient landscape in which early peoples may have interacted. Customarily, differences between the Pleistocene and modern faunas have been attributed to climate change or human-impact driven extinctions. Mexico’s Pleistocene mammal record is analyzed in time and space, emphasizing the study of the Rancholabrean Chronofauna, which is the most recent North American Land Mammal Age fauna. Palynological and paleosol records are reviewed as an independent check of the interpretation derived from mammals. The integration of the information provides the basis for a proposal regarding Late Pleistocene climate change trends across the country, and whether people were involved in the mammalian community response to climate change in terms of extinction or biogeographic shifting within and outside the country. This approach supports an explanation of the differences between southern North America’s Pleistocene and modern mammal faunas.