Fort Mohave was originally named Camp Colorado when it was established on April 19, 1859 by Lieutenant Colonel William Hoffman during the Mohave War. It was located on the east bank of the Colorado River, at Beale's Crossing, near the head of the Mohave Valley in Mohave County, Arizona by the recommendation of Lieutenant Edward Fitzgerald Beale. After the end of the Indian Wars, the fort was transferred to the Bureau of Indian Affairs in 1890. In 1935 it was transferred to the Fort Mojave Indian Reservation; the fort is administered by the state of Arizona.

The Mohave War was an armed conflict between the Mohave people and the United States from 1858 to 1859. With the California Gold Rush of 1849, thousands of American settlers headed west through Mohave country and into California. The influx of migrants passing through, combined with simple misunderstandings, led to conflict. Fort Mohave on the Arizona side of the Colorado River was built for operations against the Mohave and was the second American military post established on the river after Fort Yuma. Eventually advantages in weaponry and tactics brought the Mohave and their allies to surrender. After the signing of a peace treaty in 1859, the Mohave no longer opposed the United States through warfare. The peace also ended a long guerrilla war between the Mohave and the Maricopa of south central Arizona.