Several tribal groups have lived in the Mojave Desert within the past 2,000 years. The northern and eastern portions, for example, were occupied by the Kawaiisu, Kitanemuk, Serrano, and Koso, and Southern Paiute bands, including the Chemehuevi. Culturally distinct, these groups nevertheless spoke related languages and had similar socioeconomic systems. Resource gathering was done in family groups over wide areas, but for at least part of each year life centered on more permanent villages. The tribes knew much about Mojave Desert resources, enabling them to gather supplies from all portions of their territories. Each tribe was further divided into extended family units that were independant of each other except for trade, intermarriage and occasional war. This loose-knit structure resulted in smaller bands rather than large tribes.

The Mohave made pottery from clay and crushed sandstone, decorating their creations with geometric designs. The art of tattooing was also important to the Mojave, who frequently adorned their faces with them. The Mohave would also make 500 km trips to the Pacific Coast to trade pottery and other goods for seashells and beads. Mojave legend holds that tribal runners could cover the distance in only a few days, traveling by way of perennial springs and the Mojave River.

The Chemehuevi tribe spoke a different language from that of the Mojave Indians. They occupied a particularly barren portion of the Mojave Desert and wrested a rough living from the open land. Like their Mojave neighbors, the Chemehuevi were highly mobile, making use of resources throughout their large territory; however, they also had settlements to which they returned regularly. To transport goods and for other purposes, they created complex, beautiful baskets from reeds and grasses. Like other Southern Paiute groups, they sometimes worked small farms.