They were one of two lineages of equines native to South America during the Pleistocene epoch, alongside Equus (Amerhippus) neogeus.

Although early ancient DNA analysis studies suggested a close relationship with the wild horse, Equus ferus,[1][2] this was later shown to be incorrect, with more complete sequences finding Hippidion as an outgroup to all living equines[3] and less closely related to living equines than the North American "New World stilt legged horse", Haringtonhippus francisci.

Cladogram shown below:[4] †Hippidion †Haringtonhippus Equus ferus (wild horse) †Equus ovodovi Subgenus Asinus (asses) Subgenus Hippotigris (zebras) Hippidion is part of a distinct lineage of equines belonging to the tribe Equini that are suggested to have diverged from the ancestors of living equines of the genus Equus at least 6 million years ago.

[5] It is disputed as to whether Hippidion is an exclusively South American genus or whether remains from North America are attributable to it.

[16] At the Arroyo Seco 2 site in the Argentinan Pampas (14,782–11,142 cal yr BP), and Piedra Museo site in Santa Cruz Province, Patagonia (two separate layers dating to 12,463–10,457 cal yr BP and 15,517–12,352 cal yr BP), as well as the similarly aged Cueva del Medio site in southern Chile remains of Hippidion are associated with human artifacts, including Fishtail projectile points, and bear cut marks, indicating that they were hunted by recently arrived humans, which may have played a role in their extinction.