Seawolf left Brisbane on 21 September 1944 beginning her 15th patrol, and arrived at Manus on 29 September. Leaving Manus on the same day, Seawolf was directed to carry certain stores and army personnel to the east coast of Samar.

On 3 October, Seawolf and Narwhal exchanged SJ Radar recognition signals at 0756. On 4 October, Seawolf was directed to report her position. She failed to do so.

During her first 14 patrols, Seawolf sank 27 enemy ships, and damaged 13. This gave her total tonnage for ships sunk and damaged of 108,600 and 69,600, respectively. On the day the war began, she started patrolling in the vicinity of northern Luzon, but returned with no damage to her credit. Her 2nd patrol was the passage from Manila to Port Darwin and Seawolf did not meet any enemy ships. On her 3rd 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 4th run, Seawolf sank a transport and davmage three light cruisers, two transports, and a freighter. She received the Navy Unit Commendation for this patrol. Returning to the Philippine area for her 5th patrol, Seawolf sank a freighter. In the Makassar Strait for her 6th patrol, Seawolf sank a tanker and a freighter-transport, while she damaged a tanker.

On her 7th patrol, Seawolf 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 two other freighter-transports and damaged a freighter on this patrol. On her 8th patrol, in the Bonins-Fomrosa area, Seawolf sank a large freighter, a tanker, two sampans, and, on 23 April 1943, patrol boat #39, a converted japanese destroyer. Going to an area off the China coast north of Formosa for her 9th patrol, Seawolf sank a freighter-transport and a sampan, and damaged a destroyer escort.

Seawolf's 10th 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 11th patrol in the South China Sea and sank a larger 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 12th war patrol. Seawolf's mission on her 13th patrol was a photographic reconaissance of Palau. She also rescued two downed aviators during a US carrier air raid there. On her 14th patrol, Seawolf delivered cargo to guerilla activities in the Philippines.

Four Texans are "Still on Patrol" with Seawolf