Brandon served with the Confederate States Army from 1861 until 1864. He fought in several major battles, such as the Battle of Malvern Hill, where he was greatly injured after a ball passed through his ankle. He also participated in the Yorktown siege of 1862, the Battle of Williamsburg and the campaigns of Chattanooga and Knoxville. Brandon was promoted to the rank of brigadier general in June 1864. From July 1864 until the end of the war, he served in such positions as the commander of the Reserve Corps of Mississippi and the head of the Confederate Bureau of Conscription.