At the beginning of the Civil War, he was appointed a captain in the 10th Indiana Infantry and was promoted to colonel in less than a month. He commanded a brigade in the Army of the Ohio at the Battle of Mill Springs in 1862 and was promoted to brigadier general on March 24, 1862, based on his actions there. General Manson was wounded in the thigh and captured by Confederate forces at the Battle of Richmond, Kentucky. He was exchanged two months later and fought Morgan on his raid into Ohio. In the span of two months, Manson advanced from brigade, to division and then to command the XXIII Corps. He led the corps during the Knoxville Campaign seeing action at Campbell's Station and Knoxville. General Manson returned to brigade command, in the Army of the Ohio, during the Atlanta Campaign and was seriously wounded in the Battle of Resaca, Georgia.