The varied landscape within the river’s middle and upper watershed has many life zones that host a diversity of plant and animal life, including tropical species, unique desert species, and mountaintop survivors from the last Ice Age. The valley is known for its variety of birds, butterflies, lizards, and other wildlife, and contains many popular bird-watching spots.

This is one of America’s longest-inhabited regions, with traces of human occupation extending back more than 12,000 years. The people who live here today represent several cultures, both native and immigrant, that maintain their own distinct identities but also influence each other. The Santa Cruz Valley is the homeland of the Tohono O’odham (the Desert People), a Native American tribe that has lived here since very ancient times, and the Yaqui (Yoeme) Indians.