Born in Detroit, Michigan, Macomb was the son of Major General Alexander Macomb, who served as commanding general of the United States Army. He joined the navy in 1834 as a midshipman, and was promoted to lieutenant in 1847. He married Mary Eliza Stanton (his sister's step-daughter) on 17 January 1844 in Fort Hamilton, New York.
Macomb served with distinction during the Civil War, being promoted to commander in 1862. He took part in the riverine warfare along the Mississippi, commanded Shamrock in the North Atlantic Blockading Squadron, led the naval force which captured Plymouth, North Carolina, and led an expedition up the Roanoke River in North Carolina. For his gallantry in action with the North Atlantic Squadron, he was promoted to captain in 1866, and finally to commodore in 1870.
He was an Original Companion of the Military Order of the Loyal Legion of the United States.