This subspecies is unique to the Grand Canyon on either side of the Colorado River in northwestern Arizona. They primarily use riparian ecosystems in the canyon floor, but can also be found in talus (exposed rocky slopes) and mesquite-scrubland.

Grand Canyon Rattlesnakes are generalist predators, taking any available prey (usually rodents and lizards).

Their range is located entirely within the range of Grand Canyon National Park, which gives them a level of legal protection against harassment and persecution from humans.

An element from the venom of this species, CoaTx-II, was found to have both antibacterial properties and has the potential to treat high blood pressure. These relatively new findings may lead to promising new drugs particularly against antibiotic-resistant bacteria!