This rodent usually inhabits rough desert landscapes of boulders, washes, rocky slopes, coarse soil, and sparse vegetation characteristic of the lower Sonoran life zone. On islands it prefers rocky desert (Wilson and Ruff 1999).

Little is known about the natural history of the spiny pocket mouse despite its wide range and the many reports of its occurrence. It is nocturnal, thereby escaping the intense heat and aridity of the desert during the day. Its diet probably consists of seeds and it may eat green vegetation following the brief periods of rain. Because water is scarce in its habitat much of the time, this rodent probably finds water derived from its food. The only record of reproduction detailed the occurrence of four embryos in one specimen. Nothing is known about growth, development, physiological function, and behavior (Wilson and Ruff 1999).

This species occurs in southern Nevada, southeast California (USA) south to the cape of Baja California Peninsula (Mexico); also occurs on many islands in the Gulf of California (Patton 2005). It occurs at elevations up to 900 m (Wilson and Ruff 1999).

In the Gulf of California this species is found on Espiritu Santo Island, San Francisco Island, San Jose, Carmen, Coronados, San Marcos, San Lorenzo, Angel de la Guarda, Mejia islands, and in the Pacific on Margarita Island.

There are no known conservation measures specific to this species. However, there are several protected areas within its range.