The submarine sailed from Midway 23 September 1942 on her third war patrol, bound for the eastern coast of Kyushu. On 8 October, she contacted a convoy of four freighters, and defied the air cover guarding the ships to sink one of the cargo ships before bombs forced her deep. The next day she sank another freighter, and on the 13th underwent a severe depth charging from several escorts after she had attacked a cargo ship. Later in the patrol, she sank one of three air-escorted cargo ships, and damaged at least two more ships before completing her patrol at Pearl Harbor 8 November.
On her fourth war patrol, between 29 November 1942 and 24 January 1943, Drum carried out the demanding task of planting mines in heavily traveled Bungo Suido. On 12 December, she contacted a carrier, Ryuho, with a full deckload of planes. Although taking water forward because of faulty valves, Drum launched torpedoes at this choice target, scoring two hits, and causing the carrier to list so far that her flight deck became completely visible. Also visible was a destroyer bearing down, and splashed that indicated Drum's periscope was under fire. As the submarine dove, she lost depth control and her port shaft stopped turning. As she made emergency repairs, she underwent two waves of depth charging. When she surfaced several hours later to see what had become of her prey, and airplane forced her down. Later during this patrol, Drum damaged a large tanker, another choice target.
After a thorough overhaul at Pearl Harbor, Drum made her fifth war patrol between 24 March and 13 May 1943, searching the waters south of Truk after she had made a photographic reconnaissance of Nauru. She sanketwo freighters in April, then refitted at Brisbane, Australia. Her sixth war patrol, between 7 June and 26 July, found her north of the Bismarck Archipelago, sinking a cargo-passenger ship on 17 June. Again she put into Brisbane to replenish, and on 16 August sailed on her seventh war patrol. Adding to her already impressive list of sinkings, she sent a cargo ship to the bottom on 31 August, as well as patrolling off New Georgia during landings there. She put in to Tulagi from 29 September to 2 October to repair her gyrocompass, then sailed on to Brisbane.
Drum sailed 2 November 1943 for her eighth war patrol, coordinated with the landings at Cape Torokina. Patrolling between the Carolinas and New Ireland, she sank a cargo ship on 17 November, and on 22 November attacked a convoy of four freighters. The convoy's escorts delivered three depth charge attacks, the second of which damaged her conning tower heavily. Ordered to earl Harbor Drum reached there on 5 December; after inspection showed that the conning tower needed to be replaced, she sailed to the west coast.
Returning to Pearl Harbor 29 march 1944, Drum sailed 11 days later on her ninth war patrol, during which she patrolled the waters around Iwo Jima and other islands in the Bonins. No worthy targets were contacted, but a reconnaissance of Chichi Jima gained valuable intelligence for bombardment of the island later by surface ships. The submarine refitted at Majuro between 31 May and 24 June, then sailed on her 10th war patrol to give lifeguard service for raids on Yap and Palau. She sank a 25 ton sampan on 29 July, capturing two prisoners with whom she arrived at Pearl Harbor 14 August. She sailed for Surigao Strait 9 September on her 11th war patrol, and after 2 weeks in the Strait with no contacts was ordered north the South China Sea. Here she patrolled during the Leyte landings and the decisive Battle for Leyte Gulf, sinking three cargo ships bound to reinforce the Japanese fighting to keep the Philippines. While bound for Majuro for refit, Drum searched east of Luzon Strait for downed aviators.
Drum replenished and made repairs at Majuro between 8 November 1844 and 7 December, then sailed on her 12th war patrol for the Nansei Shoto. Only one contact was made during this patrol, from which she returned to Guam 17 January 1945. During her 13th war patrol, from 11 February to 2 April, Drum played a part in the assaults on both Iwo Jima and Okinawa, providing lifeguard service for air strikes on the Nansei Shoto and the Japanese home islands as bases were neutralized before both invasions. Returning to Pearl Harbor, Drum sailed o to a west coast overhaul, and after training at Pearl Harbor, cleared Midway 9 August on what would have been her 14 war patrol. She proceeded to Saipan at the end of hostilities and from there sailed for Pearl Harbor, the Canal Zone, and Portsmouth, N.H.
Drum was decommissioned 16 February 1946, and on 18 March 1947 began service at Washington, DC to member of the Naval Reserves in the Potomac River Naval Command which continued through 1962.
Of Drum's 13 war patrols, all save the second, ninth, and last two were designated "successful." She received a total of 12 battle stars for World War II service. She is credited with sinking 15 ships, a total of 80,580 tons of enemy shipping.