Unlike the smaller, contemporaneous Camelops, Titanotylopus had relatively broad second phalanges, suggesting that it had true padded "cameltoes", like modern camels.

It has been found at Grand View, Red Light fauna of the Love Formation, Hudspeth County, Texas, Donnelly Ranch, White Rock, Kansas, Mullen II (Kansas), Sandahl Local Fauna (Nebraska), Vallecito Creek, Colorado and 111 Ranch, Arizona in North America.

[4][5] Like modern camels, it possessed a hump for fat storage; evidence for this is provided by the long neural spines on its thoracic vertebrae.

Harrison (1985) followed Voorhies and Corner in advocating the use of Titanotylopus for only T. nebraskensis, based on a lower jaw, and Gigantocamelus for G. spatulus, which includes G. fricki.

There is a clear difference between the proximal phalanx of specimens assigned to Gigantocamelus and to Titanotylopus, based on skeletons associated with skull material.