In the fall of 1861, Commander Drayton was placed in command of the gunboat Pocahontas, in which he participated in the capture of Port Royal, South Carolina. He then became commanding officer of the sloop of war Pawnee and was active in inshore operations in the waters of South Carolina, Georgia and northern Florida through the summer of 1862. He was promoted to captain in July of that year. In September 1862, he was given command of the ironclad Passaic, overseeing her outfitting and working with John Ericsson to improve elements of monitor design. Drayton commanded his ship in attacks on Forts McAllister and Sumter in March and April 1863, experiences that reinforced his opinion concerning the limitations of the monitor type when fighting against well-defended fortifications.
Captain Drayton’s next assignment was as Superintendent of Ordnance at the New York Navy Yard. In December 1863, he began a year as Fleet Captain to the commander of the West Gulf Blockading Squadron, Rear Admiral David Glasgow Farragut. Also commanding the squadron flagship, the big sloop of war Hartford, he took part in the August 1864 Battle of Mobile Bay and the following operations within Mobile Bay. Appointed Chief of the Bureau of Navigation in late April 1865, Captain Drayton was taken sick and died at Washington, D.C., on 4 August 1865.