The valley was inhabited in late prehistoric times by the Timbisha (also called Panamint or Koso) in the extreme south end around Owens Lake and by the Eastern Mono (also called Owens Valley Paiute) in the central and northern portions of the valley. The Timbisha speak the Timbisha language, classified in the Numic branch of Uto-Aztecan language family. The closest related languages are Shoshoni and Comanche. The Eastern Mono speak a dialect of the Mono language which is also Numic, but is more closely related to Northern Paiute. The Timbisha presently live in Death Valley at Furnace Creek although most families also have summer homes in the Lone Pine colony. The Eastern Mono live in several colonies from Lone Pine to Bishop. Trade between Native Americans of the Owens Valley between coastal tribes such as the Chumash has been indicated by the archaeological record.
In 1845 John C. Fremont named the Owens valley, river and lake for Richard Owens, one of his guides. Camp Independence was established on Oak Creek nearby modern Independence, California on July 4, 1862 during the Owens Valley Indian War.