Though nearly contiguous with the Organ Mountains to the south, separated by St. Augustine Pass (elevation 1,717 m (5,633 ft)) and U.S. Highway 70, the two are very distinct geologically and botanically.

The San Andres Mountains are comparatively dry and do not support extensive woodlands.

The San Andres Mountains form part of the eastern edge of the rift valley of the Rio Grande, and are made up of west-dipping fault blocks made primarily of San Andres Formation limestone, but also with extensive exposures of reddish Abo Formation sandstone on the western side, and quartz monzonite on the eastern side.

[1] Gypsum deposits washed from these mountains are the main source of the dunes in White Sands National Park.

[3] An area of 57,215 acres (231.54 km2) in the southern portion of the San Andres Mountain range was set aside in 1941 as the San Andres National Wildlife Refuge[4] to help preserve the desert bighorn sheep, which at the time numbered 33.