On the day the war began she started patrolling in the vicinity of northern Luzon, but returned with no damage to her credit. Her second patrol was the passage from Manila to Port Darwin and Seawolf did not meet any enemy ships. On her third patrol Seawolf transported a cargo of .50-caliber antiaircraft ammunition to Corregidor in January 1942 and then took passengers from there to Surabaya. Patrolling the vicinity of Lombok Straits for her fourth run, Seawolf sank a transport and damaged three light cruisers, two transports and a freighter. She received the Navy Unit Commendation for this patrol. Returning to the Philippine area for her fifth patrol, Seawolf sank a freighter. In the Makassar Strait for her sixth patrol, Seawolf sank a tanker and a freighter-transport, while she damaged another tanker.
On her seventh patrol, she made the passage from Fremantle to Pearl Harbor, patrolling at Davao Gulf, Palau, and Yap enroute. She sank the Japanese freighter-transport Sagami Maru 40 miles inside the mouth of Davao Gulf on 3 November 1942. In addition, Seawolf sank a large freighter, a tanker, two sampans, and, on 23 April 1943, Patrol Boat Number 39, a converted Japanese destroyer. Going to an area off the China coast north of Formosa for her ninth patrol, Seawolf sank a freighter-transport and a sampan, and damaged a destroyer escort.
Seawolf's tenth patrol was in the East China Sea in August and September 1943; here she sank three large freighters and two sampans, while she damaged a third sampan. She conducted her eleventh patrol in the South China Sea and sank a large freighter-transport and an unidentified ship, and damaged a freighter. In the East China Sea north of Formosa, Seawolf sank a freighter-transport, three freighters and damaged three more freighters on her twelfth war patrol. Seawolf's mission on her thirteenth patrol was a photographic reconnaissance of Palau. She also rescued two downed aviators during an U.S. carrier air raid there. On her fourteenth patrol, Seawolf delivered cargo to guerrilla activities in the Philippines.
Seawolf began her 15th and final patrol leaving Brisbane on 21 September 1944, under the command of Lieutenant Commander A.M. Bontier, and arrived at Manus on 29 September. Leaving Manus on the same day, she was directed to carry certain stores and Army personnel to the east coast of Samar.
On 3 October Seawolf and USS Narwhal exchanged SJ radar recognition signals at 0756. Later the same day an enemy submarine sank USS Shelton (DE-407). Since there were four friendly submarines in the vicinity of this attack, they were directed to give their positions and the other three did, but Seawolf was not heard from. On 4 October, Seawolf again was directed to report her position, and again she failed to.
USS Rowell (DE-403) and an aircraft attacked a submarine in the vicinity of the attack on Shelton, having at that time no knowledge of any friendly submarines in the area, and it was thought that Seawolf must be held down by these antisubmarine activities. It is possible that Seawolf was the submarine attacked.
The report from Rowell indicates that an apparently lethal attack was conducted in conjunction with a plane which marked the spot with dye. Rowell established sound contact on the submarine, which then sent long dashes and dots which Rowell stated bore no resemblance to the existing recognition signals. After one of the several hedgehog attacks a small amount of debris and a large air bubble were seen. It has been established that the Japanese submarine RO-41 sank Shelton on 3 October, and was able to return to Japan.
In view of the above facts, and the fact that there is no attack listed in the Japanese report of antisubmarine attacks which could account for the loss of Seawolf, it is possible that she was sunk by friendly forces in an antisubmarine attack on 3 October 1944. It is also possible that she was lost due to an operational casualty or as a result of an unrecorded enemy attack. 62 officers and crew, and 17 Army passengers were lost.
See USS Seawolf for other submarines of this name.