The modern pronghorn is one of the fastest-running mammals. At full speed, a pronghorn can reach 85-95 kilometers per hour, and can maintain a speed of 65 kilometers per hour over at least 10 kilometers. Adult pronghorns can easily outrun any potential predator; their incredible speed is thought to be the result of an evolutionary arms race with the now extinct North American cheetah (Felix trumani).

The "horns" of the pronghorn are of special interest. Each horn is comprised of a slender, laterally-flattened blade of bone which grows from the frontal bones of the skull, forming a permanent core. As in the Giraffidae, skin covers the bony cores, but in the pronghorn it develops into a keratinous sheath which is shed and regrown on an annual basis. Unlike the horns of the family Bovidae, the horn sheaths of the pronghorn are branched, each sheath possessing a forward pointing tine (hence the name pronghorn). The horns of males are well developed; in females, they are either small, misshapen, or absent.

The orbits (eye sockets) are prominent and sit high on the skull; there is never an antorbital pit. The feet have only two digits; no dewclaws are present. A gall bladder is present. The teeth are hypsodont, and the dental formula is I 0/3, C 0/1, P 3/3, M 3/3 x 2 = 32.