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A desert branch of the Serrano Native Americans called the Vanyume or Beñemé, as Father Garcés called them, lived beyond and along much of the length of the Mojave River, from the east of Barstow to at least the Victorville region, and perhaps even farther upstream to the south, lived along the river for up to 8, 000 years.
The Indian trail, later the immigrants ' Mojave Road, paralleled the river from Soda Lake to the Cajon Pass.
Native Americans used this trade route where water could easily be found enroute to the coast.
Garcés explored up the length of the Mojave River in early 1776.
He called the river Arroyo de los Mártires (" river of the martyrs ") on March 9, 1776 but later Spaniards called it Río de las Ánimas (" spirit river or river of the ( lost ) souls ").
Jedediah Smith was the first American to travel overland to California by following the Mojave Indian Trail in 1826, and he called the river the Inconstant River.
John C. Frémont named the river Mohahve after the Mohave people on April 23, 1844, even though they lived two mountain ranges away on the Colorado River, as he had met six travelling Mohaves that day.
Some early Mormon ranchers called it the Macaby River.

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