The extinction of the Quaternary megafauna stands out among the evolutionary history of Cenozoic mammals. In South America, nearly 80% of the megamammals went extinct, including the native ungulates Macrauchenia patachonica and Xenorhinotherium bahiense. Little is known about the causes of the macraucheniids’ extinction and their paleobiology. Here, we have reconstructed the dietary habits of M. patachonica and X. bahiense using enamel microwear and occlusal enamel index analyses, and also inferred their niches using species distribution modeling and stable isotope paleoecology, in addition to enamel microwear and occlusal enamel index data. We found that both macraucheniids had grazer-feeding habits, although their environmental requirements were different. M. patachonica could live in colder temperatures and arid, subtropical/temperate ecosystems, while X. bahiense was adapted to warmer temperatures and more humid, semi-arid tropical environments. Thus, despite similar feeding habits, these macraucheniids had distinct environmental requirements and ecological niches, which might explain the disjunction in the South American records.