Fort Reno was established as a permanent post in July 1875, near the Darlington Indian Agency on the old Cheyenne-Arapaho reservation in Indian Territory, in present-day central Oklahoma. Named for General Jesse L. Reno, who died at the Battle of South Mountain, it supported the U.S. Army following the Cheyenne uprising in 1874.

Following the Indian Wars the fort remained to protect the more peaceful Five Civilized Tribes from the Plains Indians farther west. Soldiers from Fort Reno also attempted to control Boomer and Sooner activity during the rush to open the Unassigned Lands for settlement. Among the units stationed here were the famed Ninth Cavalry of Buffalo Soldiers.