This order, known only from South America, was common and varied in early faunas and persisted, in decreasing variety, into the Pleistocene. Early forms are near the condylarths, to such an extent that the litopterns might be considered merely as surviving and diversely specialized condylarths. They are suspected of being descended from South American condylarths, and therefore to have the same source as the latter. However, there is a growing number of scientists who believes the Litopterna (together with other South-American ungulates) originated completely independent from the other ungulates, thus are unrelated to the condylarths. They proposed a new clade to contain these groups: the Meridiungulata. Macrauchenia was the youngest genus of litopterns, and was the only litoptern group to survive the Great American Interchange; it died out during the Pleistocene.
The Litopterna, like the notoungulates and pyrotheres, are examples of ungulate mammals that arose relatively independently in "splendid isolation" on the island continent of South America. Like Australia, South America was isolated from all other continents following the breakup of Gondwana. During this period of isolation, unique mammals evolved to fill ecological niches similar to other mammals elsewhere. The Litopterna occupied ecological roles as browsers and grazers similar to horses and camels in Laurasia.
This tree shows a proposed ancestry of several mammals including the Litopterna: