After shakedown training, Drum set out to join the war in the Pacific, which began with the Japanese attack on Pearl Harbor on 7 December 1941.

An Allied aircraft mistook her for a German U-boat and attacked her as she made the transit from the United States East Coast to the Panama Canal,[9] probably in March 1942.

[10] Drum's second war patrol, which she made in the waters between Truk and Kavieng from 10 July – 2 September, found her efforts frustrated by poor torpedo performance, but she damaged one freighter before returning to Midway to refit.

On 8 October, she contacted a convoy of four freighters, and defying the air cover guarding the ships, sank the 5652 ton cargo/passenger ship IJA Hague Maru laden with 4000 tons of wheat, machines, steel, oil, automobiles and captured paper money for the Formosa bank, before aerial bombs forced her deep.

On her fourth patrol, 29 November 1942 – 24 January 1943, Drum carried out the demanding task of planting mines in heavily traveled Bungo Suido.

Although taking water forward due to 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.

After a thorough overhaul at Pearl Harbor, Drum made her fifth war patrol, 24 March – 13 May, searching waters south of Truk after she had completed a photographic reconnaissance of Nauru.

She damaged the 6439 ton cargo ship Yamagiri Maru, carrying a load of raw materials for the war effort, with two torpedoes on 28 August.

Adding to her impressive list of sinkings, she sank the 1334 ton cargo ship Hakutetsu Maru 13 on 8 September, as well and patrolled off New Georgia during the landings there.

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 from 31 May – 24 June, then sailed on her 10th war patrol to give lifeguard service for raids on Yap and Palau.

Drum replenished and made repairs at Majuro from 8 November – 7 December, then sailed for the Nansei Shoto on her 12th war patrol.

During her 13th war patrol, from 11 February – 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.

As of 2015[update], the Drum's restoration has progressed, including the complete rebuilding of part of the bow and stern sections and the installation of new I-beams inside the ballast tanks to support the submarine's overall weight.