Steaming from New Orleans 1 March, she operated out of Balboa, Canal Zone, for several weeks and departed for Pearl Harbor 2 April 1944.

On the night of 30 May the submarine encountered heavily escorted cargo vessel Shisen Maru, and scoring two hits sent her to the bottom.

She evaded counter-attacks by the screen ships and headed south for rendezvous with a wolf pack of four submarines under the command of Comdr.

On the night of 2 June Guitarro made a moonlight periscope approach and launched two torpedoes at the frigate Awaji, sinking her immediately.

Departing on her second war patrol 21 July 1944, Guitarro set course for the South China Sea off the west coast of Luzon.

She commenced her approach to the lead escorts of a large convoy 7 August and after missing the first target scored three hits on frigate Kusakaki, blowing off her bow and sinking her in a spectacular explosion.

While submerged the morning of 21 August Guitarro heard a distant depth charge attack, and soon sighted the smoke of a convoy.

Hampered by an unfavorable current and a radically maneuvering convoy, she was unable to mount an attack on two tankers; but a cargo ship turned into her and received four torpedoes as a reward.

Passenger-cargo ship Uga Maru (4,433 tons) was sunk, and Guitarro escaped amid a violent depth charge attack.

The versatile submarine, finding the water too shallow for a torpedo attack, surfaced 27 August to engage three coastal tankers with her deck gun and succeeded in sinking Nanshin Maru.

She sighted the Japanese Central Force under Admiral Takeo Kurita on the night of 23 – 24 October and tracked the ships through Mindoro Strait, unable to close for an attack.

Pounded by torpedoes from the other boats, Kumano was finally stopped, towed ashore by one of her sisters, and eventually finished off by carrier aircraft 25 November 1944.

After putting in at Mios Woendi 17 January 1945 for repairs, she made an attack with undetermined results on a convoy off Cape Batagan.

Guitarro subsequently recommissioned 15 May 1954 and commenced the training of Turkish sailors prior to transfer to Turkey under the Military Defense Assistance Program.