Leslie Canyon National Wildlife Refuge lies at the junction of the Swisshelm Mountains to the north and the Pedregosa Mountains to the south and east.  Leslie Creek does not always have water in it but it was a tributary of Whitewater Draw in the Sulphur Springs Valley, which itself is a tributary of the Río Yaqui.  The Rio Yaqui is a large river that historically drained portions of southeastern Arizona and southwestern New Mexico in the United States, as well as eastern Sonora and western Chihuahua in Mexico.  It is the remaining portions of this once-massive watershed the U.S. Fish and Wildlife Service is working to restore and protect on the Leslie Canyon and San Bernardino National Wildlife Refuges.

Between the Leslie Canyon and nearby San Bernardino Refuge, at least 334 bird species have been recorded, including many nesting birds.  In addition, 67 mammal, 43 reptile, 13 amphibian, and eight fish species have been documented.  The two refuges are critical in maintaining a sanctuary for at least 34 plant and wildlife species of concern.