The Chihuahuan Desert region is home to a multitude of specialized invertebrates. Among the most conspicuous are the desert tarantula, whip scorpions or vinegaroon, desert millipede, a number of scorpions, and giant centipede. A rich butterfly and moth fauna is also to be found here.

As with most desert regions, fish species have evolved through ages of isolation. Spring systems have become home for a multitude of unique (endemic) fish. More species of pupfish occur in the Chihuahuan Desert region than in any other desert region.

Common Chihuahuan Desert amphibians include the barred tiger salamander, spadefoot toads, and the Rio Grande frog. A recent introduction, the bullfrog, has found suitable habitat along portions of the Rio Grande, Pecos River, and in stock tanks across the region.

A great number of lizards inhabit the region. Among these are the whiptails, spinys, horned, collared, and geckos. Snakes have evolved to take advantage of a wide range of conditions. While a few are diurnal—such as the garter and coachwhips—most avoid the heat of the sun by prowling after dark. Chihuahuan snake species include the beautiful Mexican kingsnakes, Trans-Pecos ratsnake, and many species of rattlesnakes.

More species of birds have been recorded in the Big Bend National Park than in any other national park. Despite the high numbers, most are non-resident or seasonal. In addition, population densities are usually small.

Mammals are diverse and tend to be nocturnal. The northern Chihuahuan Desert region has one of the richest bat faunas to be found anywhere. Eighteen species have been documented in Presidio County, Texas, alone. Most are small and insectivorous. Notable representatives include the pallid bat, western pipistrelle, and Brazilian freetailed bat.

Mule deer, white-tailed deer, and pronghorn are common residents. Desert bighorn have been successfully reintroduced to many of the desert mountain ranges in the northern Chihuahuan Desert. Other common mammals include the coyote, collared peccary (or javelina), ringtail, black-tailed jackrabbit, spotted ground squirrel, a number of skunk species, woodrats, and many nocturnal mice. The larger predators have struggled for survival, but mountain lions still occur here and black bears are making a return to the northern Chihuahuan Desert region. Grizzly bears were found in at least one Chihuahuan Desert mountain range until the late 1960s.