After shakedown off New London, Connecticut, Pampanito transited the Panama Canal and arrived Pearl Harbor 14 February 1944. Her first war patrol (15 March to 2 May) was conducted in the southwest approaches to Saipan and Guam. She served on lifeguard duty south of Yap, then scored two torpedo hits on a destroyer before sailing for Midway and Pearl Harbor for refit and repairs to a hull badly damaged by depth charges.
Pampanito's second war patrol (from 3 June to 23 July) took place off Kyushu, Shikoku, and Honshu. On 23 June, a submerged Japanese submarine fired two torpedoes, just missing Pampanito. On 6 July, Pampanito damaged a Japanese gunboat, and 11 days later headed for Midway.
Pampanito's third war patrol (from 17 August to 28 September), a "wolfpack" operation with submarines Growler (SS-215) and Sealion (SS-315), was conducted in the South China Sea. On 12 September, she sank 10,509-ton transport Kachidoki Maru and 5135 ton tanker Zuiho Maru and damaged a third ship. On 15 September, with Sealion and later, Barb (SS-220) and Queenfish (SS-393), she helped rescue British and Australian survivors of a POW ship sunk while enroute from Singapore to Formosa. She then set course for Saipan, disembarked the survivors, and steamed on to Pearl Harbor.
Pampanito's fourth war patrol (from 28 October to 30 December) took place off Formosa and the coast of southeastern China with Sea Cat (SS-399), Pipefish (SS-388), and Searaven (SS-196). Sinking 1200-ton cargo ship Shinko Maru No. 1, 19 November, she damaged a second ship before putting in to Fremantle for refit. Her fifth war patrol in the Gulf of Siam (from 23 January to 12 February 1945), with Guavina (SS-362), was highlighted by two sinkings, 6968-ton cargo ship Engen Maru 6 February and 3520-ton passenger-cargo ship Eifuku Maru 8 February.
Refitted at Subic Bay, Pampanito returned to the Gulf of Siam for her sixth war patrol. Operating with Caiman (SS-323), Sealion, and Mingo (SS-261), she sighted only one target before sailing for Pearl Harbor.
From Pearl Harbor the ship proceeded to San Francisco for overhaul, departing for Pearl Harbor again 1 August. With the end of the war, she was ordered to return to San Francisco. She decommissioned at Mare Island 15 December 1945. She remained in reserve until April 1960 when she was assigned to Naval Reserve Training at Mare Island. Reclassified AGSS-383, 6 November 1962, she served as a Naval Reserve Training ship at Vallejo, California, until she was stricken from the Navy Register on 20 December 1971.
Pampanito was turned into a memorial at San Francisco on 21 November 1975, and is a National Historic Landmark. She flies a broom from her mast, indicating that her last patrol was a "clean sweep": all torpedoes shot.
Pampanito has completed three maintenance drydockings since becoming a museum, and is still sea-worthy. In 1995, she played the fictional USS Stingray (SS-161) in the movie Down Periscope, sailing under her own power in San Francisco Bay and venturing past the Golden Gate Bridge. It had been fifty years since she sailed under the bridge.
Pampanito earned six battle stars for World War II service.