The eastern short-horned lizard is found in the western counties of the Dakotas to northeastern Montana and adjacent Canada, south to eastern Colorado and extreme northeastern Utah. The species is locally common in the semi-arid short grass plains of the extreme western portion of Nebraska. In North Dakota the eastern short-horned lizards have been found along the Little Missouri River and Knife River drainages. The eastern short-horned lizard frequents shortgrass prairie, sagebrush, open rocky or sandy plains, and open pinon-juniper, pine-spruce, and spruce-fir forests. Typically, the species inhabits hot dry or semiarid regions, such as the shortgrass plains in rather rough terrain. The soils may be stony, sandy, or firm, but usually some fine loose soil is present. The species is often found under or around sagebrush plants.

The eastern short-horned lizard is active during daylight hours from late spring to fall. The species spends a considerable amount of time basking in the sun, which is crucial for digestion. Eastern short-horned lizards will bury themselves in the soil on cloudy days and also to hibernate for the winter. The eastern short-horned lizard, when chased by a predator, stops, and lowers its body flat to the ground to camouflage itself into the soil. A unique defense mechanism used by the species is its ability to squirt blood from the corners of its eyes. The eastern short-horned lizard has a reproductive style (ovoviviparous) different from most lizards. The species carries its young in a transparent membrane. In late July or August, the membrane breaks open and five to 36 young are born. The diet of the species consists of a variety of ants, spiders, beetles, snails, grasshoppers, and sowbugs.