- For the river in Argentina see Santa Cruz River (Argentina)
- For the river in the Philippines see Santa Cruz River (Philippines)
The Santa Cruz River is a river in southern Arizona, United States, and northern Sonora, Mexico. The Santa Cruz has its headwaters in the high intermontane grasslands of the San Rafael Valley to the east of Patagonia between the Canelo Hills to the east and the Patagonia Mountains to the west, just north of the U.S.-Mexican border. It flows southward into Mexico and turns westward, and reenters the United States just to the east of Nogales. It then continues northward from the International border at Nogales past the Tumacacori National Historical Park, Tubac, Green Valley, Sahuarita, San Xavier del Bac, and Tucson to the Santa Cruz Flats just to the south of Casa Grande and the Gila River. Between Nogales and Tucson the river valley is flanked by the Patagonia and Santa Rita Mountains on the east and the Tumacacori and Sierrita Mountains on the west. The Santa Cruz River is usually a dry riverbed through much of the year, unless the area receives significant rainfall.
