This southwestern rattlesnake species can get very large, up to about 7 feet long, though generally they are much smaller. They are generalist predators as juveniles, while they grow into primarily mammal-specialist predators as adults. Western diamondbacks are important predators for rabbits, gophers, and other medium-sized mammals. They are easily distinguished from many other rattlesnake species by their stark black-and-white tail before their rattle.

The western diamondback rattlesnake occupies a diverse range of habitats from sea level to 7000 feet elevation.

Western diamondbacks are still subject to intense human persecution (including "rattlesnake round-ups") where hundreds of individuals (including juveniles and gravid females) are killed.

The status of this species is disputed in the US state of Kansas, where individuals have been collected - both within and outside of suitable habitat. Some authorities suspect these to be the result of human introductions, while others believe a native population is present in a small area near the Oklahoma border.