It is likely that "Macrauchenia" evolved from earlier litopterns "Theosodon" or "Promacrauchenia", or a similar species. Litopterna was one of the five (four in some classifications) ancient orders of endemic South American mammals collectively called Meridungulates. Their relationships with other mammal groups outside South America have been poorly understood, as their early evolutionary history would have been in Western Gondwana, and outside of South America this area is now Antarctica. When South America separated from Antarctica in the Eocene, meridungulate orders survived in South America in isolation. Most flourished in the Paleogene and then diminished. Formerly, North American paleontologists considered them inferior to Northern Hemisphere taxa and to have been outcompeted to extinction in the Great American Biotic Interchange after the establishment of the Central American land bridge. However, more recent evidence shows that three of the meridungulate orders declined long before, just as happened to early mammal groups elsewhere. Litopterns and notoungulates continued, evolving into a variety of more derived forms. While toxodontid notoungulates expanded into North America during the GABI, litopterns remained confined to South America. "Macrauchenia" was among the last surviving meridungulates, along with litopterns such as "Neocaliphrium" and the large notungulates "Toxodon" and "Mixotoxodon". These last endemic South American hoofed animals died out at the end of the Lujanian (10,000-20,000 years ago).