Among the last gomphotheres along with the South American Notiomastodon, it became extinct as part of the end Pleistocene-extinction event, approximately 12,000 years ago, along with most other large mammals in the Americas.

The first remains of this species were recovered from Ecuador by Alexander von Humboldt, at a location the local population referred to as the "Field of Giants".

However, by the 1930s, general agreement had shifted to regard both forms as representing a single, geographically widespread species, with Cuvieronius humboldtii considered to be the correct name.

This situation went unaddressed until 2009, when Spencer Lucas petitioned the International Commission on Zoological Nomenclature to officially change the type species of Cuvieronius to M. hyodon as had been followed for over 50 years by that time, rather than abandoning the well-known Cuvieronius as a synonym, as well as to designate the specimen MNHN TAR 1270, a skull and lower jaw from Tarija, Bolivia, as the neotype specimen of the genus/species.

[12] In 1982, Daniel H. Janzen and Paul Schultz Martin suggested that the diet of Cuvieronius probably included fruit, and that it was likely an important seed disperser of a variety of Neotropical plants with large fleshy fruits similar to those consumed by large animals in Africa, but which lack effective living native seed dispersers, which they described as "Pleistocene anachronisms".

[18][7] It is considered closely related to, if not derived from, Rhynchotherium, a North American gomphothere genus known from the Late Miocene and Pliocene.

[4] Some authors have suggested that the genus first appeared around 2 million years ago, with its earliest fossils found in Florida,[15] while other authors suggest the earliest unambiguous appearance of Cuvieronius in the fossil record in North America dates to somewhat later, around 1.4 million years ago (Ma).

[21] Remains found near the town of Hockley in Texas near Houston, which date to around 24,000 years Before Present (BP), are the most recent findings north of Mexico.

[22] Cuvieronius was extirpated from South America by the end of the Late Pleistocene, with its youngest dates on the continent being around 44,000 years ago, before the arrival of people.

At the El Fin del Mundo kill site in Sonora, Mexico, remains of an individual of Cuvierionius and another indeterminate gomphothere were found associated with Clovis spear points, suggesting that hunting may have played a role in its extinction.