[1][2] The first described remains of Bison antiquus were collected at Big Bone Lick, Kentucky in Pleistocene deposits in the 1850s and only consisted of a fragmentary posterior skull and a nearly complete horn core.

[8] Unlike living American bison, which are almost exclusively grazers,[16] dental wear analysis suggests that Bison antiquus was a variable mixed feeder (both browsing and grazing) with an adaptable diet depending on geographical location, with diets varying from strict grazing to mixed feeding.

[17][18][12] Bison antiquus was likely preyed upon by large carnivores, which may have included the American lion (Panthera atrox),[19] the sabertooth cat Smilodon fatalis,[20] and dire wolves (Aenocyon dirus).

[22] In North America, B. priscus evolved into the large long-horned Bison latifrons, which then gave rise to B. antiquus sometime prior to 60,000 years ago.

[24] A number of sites document the exploltation of Bison antiquus by Palaeoindian groups, such as those associated with the Clovis culture[25] and the later Folsom tradition.

A number of paleo-Indian spear and projectile points have been recovered in conjunction with the animal skeletons at the site, which is dated around 9,700 to 10,000 years ago.

[32][33] B. antiquus remains exhibiting butchery marks have been found at Ayer Pond on Orcas Island in Washington State.