First war patrol, December 1941

On 8 December 1941, S-41 was in Manila Bay. After hearing of Japan's attack on Pearl Harbor, she patrolled off Looc Bay, Tablas Island, in an attempt to impede the Japanese offensive. But the Japanese thrust continued.

Second war patrol, December 1941

S-41 returned briefly to Manila for replenishment but departed again on 24 December. Into the new year, 1942, she patrolled off the Lingayen area. On 4 January she retired from Luzon and moved south toward the Netherlands East Indies. By 12 January, she was off Tarakan; by 15 January, Balikpapan; and by 25 January, after patrolling Makassar Strait, she was at Soerabaja. On 4 February, she departed that north Java base and returned to Makassar Strait. Thirteen days later, she torpedoed a Japanese transport off Cape Mangkalihat and was credited with a kill by the American-British-Dutch-Australian Command (ABDA).

On 10 March, she concluded her patrol at Fremantle, Western Australia. The Netherlands East Indies had fallen.

Third war patrol, May 1942

Throughout the patrol, S-41’s gyrocompass had given continuous trouble, and her periscope had proven faulty. Repairs were made at Fremantle and at Brisbane, Queensland; and, on 9 May, she departed the latter port for the Solomon Islands. Encountering poor weather during the patrol, she operated in the Shortland Islands and Treasury Islands through the end of the month and returned to Brisbane on 6 June.

Fourth war patrol, July 1942

On 22 July, she headed out of Moreton Bay, returned for emergency repairs; and, on 7 August, got underway for the New Britain-New Ireland area. She fired on several enemy ships, including a submarine with probable damage, and her patrol was noted for its "absence of serious material failures" — an achievement unique in boats of her class at that time.

Moving to the Guadalcanal area later in the patrol, S-41 was operating 5 nautical miles (9.3 km; 5.8 mi) from Savo Island when a ship moving at high speed — which her commanding officer identified as a possible cruiser — passed her in the predawn darkness of 24 August 1942 after she submerged and three depth charges exploded close enough to her to shatter light bulbs. On 25 August in the same general area, she observed a destroyer passing her and heard eight depth charges explode no closer than 400 yards (370 m) from her. As the night wore on, a destroyer began searching for her with active sonar, so she cleared the area. On the evening of 25 August. she received a message ordering her to return to her patrol station, a surprise to her commanding officer, who wondered how his superiors could have known she was off station. Her crew then discovered that S-41 had missed an earlier message ordering her to a new station, leading her commanding officer to wonder if S-41 had been the subject of friendly fire attacks by Allied ships who had not expected a U.S. submarine at S-41′s location on 24–25 August 1942.^[1]

Fifth war patrol and overhaul, September 1942

At Brisbane from 2–21 September, she got underway for Hawaii on the latter date and, after patrolling in the Ellice Islands, arrived at Pearl Harbor on 13 October. On 29 October, she put into San Diego, California, and the next day began an extensive overhaul which lasted into April 1943. On 23 April of that month, she departed southern California for the Aleutian Islands.

Sixth war patrol, May 1943

Arriving at Dutch Harbor on 11 May, S-41 departed four days later and took up patrol duties off Paramushiro in the Kuril Islands, on 21 May. On 27 May, she scored a probable kill on a four-masted fishing schooner; and, in the pre-dawn darkness of 31 May, she torpedoed a cargo ship in a night surface attack. From the violent internal explosion and fires which followed the initial torpedoing, the victim was presumed to have been carrying high explosives or light, volatile liquids.

Seventh and eighth war patrol, July 1943

On 15 June, S-41 returned to Dutch Harbor. Thirteen days later, she got underway for Attu, whence she departed for the Kuril Islands on 3 July. Fog, heavy seas, sampans, fishing nets, and the erratic performance of torpedoes hindered her movements and impaired her hunting during that 33-day patrol and during her final patrol, again off Paramushiro, in late August and early September.