Aravaipa Creek is often considered the best native fish habitat in Arizona. It is the only low-desert creek in Arizona with an unprecedented seven species of native fish. Two of these, the loach minnow and spikedace, are listed as threatened under the Endangered Species Act, with designated critical habitat in the creek. Aravaipa is one of the last creeks in the state to be in pristine condition; the segment within the wilderness is mostly free of contamination by non-native fish species. The native fish found here are abundant and doing well. White-tailed and mule deer, javelina, and coyotes often drink from the creek in the evenings, leaving their distinctive tracks in the mud. Mountain lions prowl craggy peaks, but are rarely seen. Desert bighorn sheep are often visible on canyon walls high above the creek. Nearly a dozen bat species flourish in Aravaipa's small caves, emerging at dusk to hunt for insects. Troops of coatimundi travel the canyon bottoms and are a special treat.

Several species of rattlesnakes inhabit Aravaipa Canyon, so visitors should take care to avoid them. Many other snakes including harmless garter snakes can be seen. Please do not harm any snakes. A variety of frogs, notably leopard frogs, serenade campers in the evenings.

Aravaipa is famed as a birdwatcher's paradise. Nearly every type of desert songbird is found here, with more than 150 species documented in the wilderness. Saguaro and other cacti grow on Aravaipa's rocky ledges, providing nest sites for small owls, woodpeckers, and other desert birds. Mesquite-covered grassy flats furnish cover for abundant birdlife on the canyon floor. Species receiving federal and state protection include the peregrine falcon, common black-hawk, bald eagle, cactus ferruginous pygmy-owl, and southwestern willow flycatcher. Being close to Mexico, the wilderness is often visited by birds more common to lands south of the border.