After a six-week training period in New London, Conn., the submarine sailed for the Pacific Theater of Operations and joined the 7th Fleet at Brisbane, Australia, on 10 July 1943.

She topped off her fuel tanks from submarine rescue vessel Coucal on 29 July, and on 7 August took station in the scouting line in the sealanes between Truk and the Bismarck Archipelago.

The submarine trained in emergency dives, and her crew frequently went to battle stations upon the sighting of enemy aircraft; but the patrol was not enlivened by action with surface ships before the boat moored alongside Fulton in Brisbane on 13 September for refit.

Balao sighted a convoy on 17 October, but it escaped her salvo of six torpedoes by making a radical zig-zag maneuver and increasing speed to open the range.

Balao joined Silversides in a coordinated attack on a seven-ship convoy on 23 October, firing 10 torpedoes at three ships that presented an overlapping target.

Balao then shifted to the Truk-New Hanover route where she conducted an uneventful patrol until 7 November, when she headed for Milne Bay, New Guinea, for refit alongside Fulton.

The four warships maneuvered in a radical zigzag plan at a speed of 20 knots (37 km/h; 23 mph), passing the submarine so rapidly that she only managed a shot at the second cruiser.

The weather impeded her efforts to close the convoy, but also offered protection when a rain squall covered Balao while she fired six torpedoes.

A survivor was taken on board, who stated that his vessel, the 5,857-ton passenger cargo ship Nikki Maru, had gone down rapidly after being hit.

A convoy located on 26 February did not offer a chance of attack, because Gato had first fired on it causing its escorts to chase Balao from the scene.

Radar and lookouts failed to locate the merchantman, so Balao returned to patrol the shipping lanes after a very successful attack.

A fuel shortage forced Balao to enter Majuro Atoll on 12 June to begin refit alongside submarine tender Sperry.

On 26 July, Balao joined in the bombardment of Angaur Island in the Palaus by firing on a lighthouse and loading docks, scoring several direct hits.

The same day, she witnessed a fighter plane from the carrier Bunker Hill splash into the water dead ahead and quickly managed to rescue the pilot.

After transferring him to Dortch, Balao returned to lifeguard duties off Peleliu Island where she picked up two more downed aviators on 27 July.

Balao was then ordered back to the United States where she entered the Mare Island Navy Yard on 20 August for a complete overhaul.

That day proved to be lucky for Balao because, later that night, she picked up a larger ship on radar and successfully moved into position.

The target's escorts struck back at Balao with depth charges, but the submarine escaped damage and resumed patrol duty later that day.

The early morning darkness made it impossible to assess the damage, but Balao received credit for sinking Hakozaki Maru, a 10,413-ton transport.

An escort picked up the submarine's trail, and Balao ran for deep water under a smoke screen without waiting to observe results.

A small Japanese patrol vessel made an attempt to counterattack, but Balao slipped below the surface and headed for Guam to replenish her fuel, provisions, and torpedoes.

On 2 April, Balao submerged rapidly to avoid detection by a large, low-flying enemy plane and took on several feet of water in her conning tower, grounding out her radar and other electrical gear.

On 23 May, Balao's earlier mechanical difficulties rendered her stern diving planes totally inoperable, and she received orders to Pearl Harbor for refit.

A month in port readied her for sea once more, and Balao got underway on 7 July for the Nanpō Islands area and waters east of Honshū.

Her primary duty during this tenth and final war patrol was to provide lifeguard services for Allied aircrew during strikes on the Japanese home islands.

Balao rendezvoused with Peto the next day to transfer the rescued aviators, then proceeded on to Pearl Harbor, where she arrived on 25 August.

The submarine departed Pearl Harbor on 31 August for Staten Island, New York, where her crew enjoyed a well-deserved rest period and she underwent an overhaul.

There, she served primarily as a training ship for antisubmarine and Special Development Forces in the Key West and Guantánamo Bay operating areas.

After joint exercises with the navies of several South American countries, the ship made liberty calls to principal ports such as La Guaira, Venezuela; Rio de Janeiro, Brazil; Montevideo, Uruguay; Mar del Plata and Buenos Aires, Argentina.

Balao also deployed to the western Atlantic during the Cuban Missile Crisis in October–November, but returned to routine training duty when the trouble died down.