It is bordered to the north and to the west by the Barry M. Goldwater Air Force Range, to the south by Mexico's El Pinacate y Gran Desierto de Altar Biosphere Reserve, to the northeast by the town of Ajo, and to the southeast by Organ Pipe Cactus National Monument.

The area is an active corridor for illegal entry and smuggling into the U.S.[4] Since 2017 the skeletal remains of at least forty people have been found here, migrants crossing who died due to lack of water and/or from extreme temperatures.

[8] Author Edward Abbey, a frequent visitor, described the refuge as "the best desert wilderness left in the United States"[9] and is reputedly buried there.

[10] Parts of the refuge are sometimes temporarily off-limits to visitors during training exercises on the adjacent Barry M. Goldwater Air Force Range, or because of law enforcement concerns with respect to illegal trafficking of people and drugs from Mexico.

These fauna include:[14] In 1936, the Arizona boy scouts mounted a statewide campaign to save the desert bighorn sheep, leading to the creation of CPNWR.

The contest-winning bighorn emblem was made up into neckerchief slides for the 10,000 Boy Scouts, and talks and dramatizations were given at school assemblies and on radio.

A brick and stone monument was erected on a hill near Tule Well, and Major Burnham delivered the dedication speech opening CPNWR in 1941.