Reno was commissioned as a brigadier general in November 1861. He led an assault at Roanoke Island, North Carolina, in February 1862. Months later, in July 1862, he was promoted to Major General for his work at the Battle of Camden, NC. Afterward, Reno served in command of the 9th Corps in the Battle of First Manassas. He was mortally wounded at the Battle of South Mountain in Maryland on September 14, 1862.