Climatic and environmental changes, as well as human action, have been cited as potential causes for the extinction of megafauna in South America at the end of the Pleistocene. Among megamammals lineages with Holarctic origin, only horses and proboscideans went extinct in South America during this period. This study aims to understand how the spatial extent of habitats suitable for Equus neogeus and Notiomastodon platensis changed between the last glacial maximum (LGM) and the middle Holocene in order to determine the impact that climatic and environmental changes had on these taxa. We used species distribution modeling to estimate their potential extent on the continent and found that both species occupied arid and semiarid open lands during the LGM, mainly in the Pampean region of Argentina, southern and northeastern Brazil, and parts of the Andes. However, when climate conditions changed from dry and cold during the LGM to humid and warm during the middle Holocene, the areas suitable for these taxa were reduced dramatically. These results support the hypothesis that climatic changes were a driving cause of extinction of these megamammals in South America, although we cannot rule out the impact of human actions or other potential causes for their extinction.