The eastern twin-spotted rattlesnake can be found in scrub-oak and agave-type habitats at higher elevations in the Sierra Madre Oriental. They primarily consume vertebrates including lizards, small mammals, and young birds

They are one of several "cloud island" species which colonized temperate forested highlands during the Pleistocene epoch. Surrounding lowland areas turned arid (environments uninhabitable to these species) cut these separate populations off from one another.

This species, the twin-spotted rattlesnake, is considered imperiled in Arizona, USA. The subspecies is endemic to Mexico, however, and occurs largely in unpopulated, isolated habitat.