The hispid pocket mouse occurs across the Great Plains from southern North Dakota to central Mexico, and west from the Missouri River to the foot of the Rocky Mountains.

There are four recognized subspecies: Hispid pocket mice inhabit a variety of upland habitats, but are most abundant in areas with sandy soils and patches of bare ground.

Hispid pocket mice are not found in rocky prairie, and seem to avoid sand dunes and riparian zones.

Essentially granivores, the diet of the hispid pocket mouse consists primarily of seeds it selectively gathers, though these mice do consume some insects and leaves.

Adult males have been recorded with enlarged testes from March through October, and pregnant females have been trapped in July and August.