The San Andres National Wildlife Refuge is located in the southern San Andres Mountains of southcentral New Mexico. The mountain range, which lies within the northernmost extension of the Chihuahuan Desert, rises to an elevation of 8,229 feet at San Andres peak. Refuge habitats vary from creosote and Chihuahuan desert grasslands in the bajadas to pinyon-juniper woodlands on the mountaintops. Numerous springs, seeps and seasonal streams provide lush riparian habitats throughout the Refuge.

There is no public access on the Refuge due to its location within the secure, military weapons testing facility of White Sands Missile Range.