It is directly east of Death Valley National Park, and is 90 mi (140 km) west-northwest of Las Vegas.

Inside Ash Meadows is Devils Hole, a detached unit of Death Valley National Park.

The refuge is a major discharge point for a vast underground aquifer water system, reaching more than 100 mi (160 km) to the northeast.

Water-bearing strata come to the surface in more than thirty seeps and springs, providing a rich, complex variety of mesic habitats.

Ash Meadows National Wildlife Refuge was established to provide and protect habitat for at least twenty-six endemic plants and animals, meaning they are found nowhere else in the world.