With the outbreak of the Civil War in 1861, Cooper pledged his allegiance to the Confederacy. In May, Secretary of War Leroy Pope Walker sent Cooper a letter authorizing him to "take measures to secure the protection of these tribes in their present country from the agrarian rapacity of the North." He raised a regiment known as the 1st Choctaw and Chickasaw Mounted Rifles and was commissioned as its colonel. Given brigade command, Cooper pursued the Creek Indian leader Opothleyahola in November and December, when the latter led his loyal Union followers toward Kansas. Cooper's brigade fought at the battles of Round Mountain and Chusto-Talasah, winning a decisive victory at Chustenahlah.