After the start of the Civil War, Gamble was appointed Lieutenant Colonel of the 8th Illinois Cavalry regiment on 18 September 1861. His nomination was urged by his close friend, U.S. Congressman John F. Farnsworth, who raised and commanded the regiment. Gamble's son George also joined the regiment as a first lieutenant. (George survived the war, but was killed in a collapsed hotel during the 1906 San Francisco earthquake).