After shakedown, Guavina was towed down the Mississippi in a floating drydock by tug Minnesota, reaching New Orleans 24 January 1944.

She underwent training exercises at New Orleans and at Balboa, C.Z., before reaching Pearl Harbor 5 April to prepare for her first war patrol.

On her second war patrol (20 June – 31 July) Guavina sailed from Majuro to Brisbane, Australia, sinking 1 ship and rescuing 12 downed aviators.

The sub spent the next 3 hours running silent and deep to avoid a total of 18 depth charges and 8 aerial bombs, surfacing at 06:43 to observe the wreckage of Tama Maru (3,052 tons).

Working first with Pampanito and then with Becuna and Blenny, Guavina spent her fifth war patrol (23 January – 5 March 1945) again in the South China Sea.

The value of the coordinated attack group was quickly proved as on 6 February Guavina was directed in for the kill by Pampanito and sank the 6,892-ton tanker Taigyo Maru.

To avoid the subsequent depth charging, Guavina pulled the unusual maneuver of lying on the bottom near the stern of her recent victim.

She returned Pampanito's favor the following day by providing a diversion in the form of four flares from her "Buck Rogers" gun as her sister sub maneuvered for a successful shot.

With no room to run, she lay on the bottom at 130 feet (40 m) while Japanese escorts and planes dropped a total of 98 depth charges and bombs during the next 7 hours.

On her sixth war patrol (21 March – 8 May) Guavina worked in coordination with Rock, Cobia, and Blenny in the South China Sea.

From March 1949, Guavina underwent extensive overhaul and modification under project SCB 39 for conversion to a submarine oiler at Mare Island, and was even equipped with a snorkel.

Operating out of Key West, Guavina cruised to the Caribbean Sea and up the East Coast to Nova Scotia to test the concepts of fueling seaplanes and other submarines, although most of her work was in the Gulf of Mexico and the Straits of Florida.

Emerging from overhaul 12 July 1957 with the new designation AOSS-362, Guavina resumed her established pattern of testing various applications of submarine oiler and seaplane refueling concepts, operating principally in the Caribbean.