Fort Reno began as a military camp in 1874 in the Indian Wars Era. It was established at the insistence of Agent John Miles at the Darlington Indian Agency, to pacify and protect the Cheyennes and Arapahos there. Troops from the 10th Cavalry (Buffalo Soldiers) were dispatched from Fort Sill, but because of other Indian unrest, were detained at the nearby Wichita Agency at present day Anadarko.
The cavalry and infantry stationed at Fort Reno played an important role in the transition of the area from Indian Territory status to Oklahoma statehood in 1907.
United States Cavalry units, including the Buffalo Soldiers (Black soldiers of the 9th and 10th U.S. Cavalry and the 24th and 25th Infantry), and the Cheyenne and Arapaho Indian Scouts, along with the U.S. Marshal Service, maintained the peace on the central plains until the turn of the century.
Fort Reno was added to the National Register of Historic Places in 1970.