Van Cleve served under Maj. Gen. George H. Thomas at Mill Springs, and was later promoted to brigadier general of volunteers on March 21, 1862, in recognition for his services at that battle. He commanded a brigade at the Siege of Corinth and a division at Perryville. He was disabled by a wound at Stones River, but returned to his division upon recovery. He fought at Chickamauga, and was in command of the post and forces at Murfreesboro, Tennessee, after the battle. He was in command of the defenses of the Nashville and Chattanooga Railroad until he was mustered out in 1865. In the omnibus promotions in 1866 following the war, he was brevetted major general, dating from March 13, 1865.