[6] Its closest living relative is the muskox (Ovibos moschatus), from which it diverged around 3 million years ago.

[8][9] Unlike today's Arctic and tundra-adapted muskoxen, with their long, shaggy coats, Bootherium was physically adapted to a range of less frigid climates, and appears to have been the only species of muskox to have evolved in and remain restricted to the North American continent (the Arctic muskox's range is circumpolar, and includes the northern reaches of Eurasia as well as North America).

[3] Bootherium was significantly taller and leaner than muskoxen found today in Arctic regions.

Bootherium was one of the most widely distributed muskox species in North America during the Pleistocene epoch.

The species went into decline, and eventual extinction, approximately 11,000 years ago, at the end of the last Ice Age.