Death Valley is home to the Timbisha tribe of Native Americans, formerly known as the Panamint Shoshone, who have inhabited the valley for at least the past 1000 years. The Timbisha name for the valley, t?mpisa, means "rock paint" and refers to the red ochre paint that can be made from a type of clay found in the valley. Some families still live in the valley at Furnace Creek. Another village was located in Grapevine Canyon near the present site of Scotty's Castle. It was called maahunu in the Timbisha language, the meaning of which is uncertain, although it is known that hunu means "canyon".

The valley received its English name in 1849 during the California Gold Rush. It was called Death Valley by prospectors and others who sought to cross the valley on their way to the gold fields, although only one death in the area was recorded during the Rush. During the 1850s, gold and silver were extracted in the valley. In the 1880s, borax was discovered and extracted by mule-drawn wagons.

Death Valley National Monument was proclaimed on February 11, 1933 by President Hoover, placing the area under federal protection. In 1994, the monument was redesignated as Death Valley National Park.