The geology of the park greatly affects the flora and fauna. Most sites above the escarpment are on the High Plains and are short-grass prairie, which includes blue grama, buffalograss and sideoats grama. The canyons in the western portion of the park support several species of juniper as well as scrub oak. The bottomland sites along the Little Red River and its tributaries support tall and mid-level grasses including Indian grass, Canada wildrye and little bluestem, cottonwood trees, wild plum thickets and hackberries. The park abounds with wildflowers in the spring and has a variety of yuccas and multiflowering cacti.
Over 12,000 years ago these lands supported now-extinct mammoth and giant bison, as well as camel and horses in a damper, cooler climate. More recently, black bears and grey wolves made their home in the region, but by the 1950s, they were forced out due to predator control by humans. Now mule and white-tailed deer, coyotes and bobcats are common with a few pronghorn antelope roaming these canyonlands.
The park is also home to the Texas State Bison Herd (the largest herd of buffalo in the state park system). In September 2011, 80 descendants of the great southern plains bison herd were released to a larger habitat of 1,000 acres of grasslands in the park. Visitors can view these indigenous animals in their native habitat.