On 18 November, Holland with Salmon, Swordfish, Sturgeon, and Skipjack arrived at Manila and formed SubDiv 21 of the Asiatic fleet to bolster defenses in the Philippines as marked tension was growing due to Japanese militarism.

On 22 December, while on the surface in Lingayen Gulf, she encountered two Japanese destroyers and pressed home an attack which seemed to bewilder the reluctant enemy.

In January 1942, she moved south to operate in the Gulf of Davao and off the southern tip of Mindanao and thence proceeded to Manipa Strait between Bura and Ceram in the Molucca Islands.

The tender Holland moved her base of operations to Exmouth Gulf, Australia, on 20 February, as Salmon set out on her second war patrol.

Salmon departed Fremantle on 21 July for her fourth war patrol in the South China Sea-Sulu Sea area.

During this patrol, Salmon was unable to gain a favorable position for successful attack, but made numerous sightings and reports of shipping movements to sister subs in the vicinity.

Salmon then maneuvered for a closer inspection and saw that the sampan was displaying rising-sun emblems on her deckhouse and her crew was attempting to jettison objects over the side.

Salmon remained at Mare Island until on 30 March 1943, undergoing alterations including the installation of new radar equipment and two 20 mm mounts to augment her firepower.

She was assigned a special photo reconnaissance mission for her tenth patrol which would assist in preparing plans for gaining control of the Caroline Islands.

Salmon's eleventh and last war patrol was conducted in company with submarines Trigger and Sterlet as a coordinated attack group in the Ryukyu Islands.

Salmon fired four torpedoes and made two good hits, but was forced to dive deep under a severe depth charge attack by escort CD-29.

The vessels began to close, but Salmon showed an aggressive stance, turned on the attackers and passing within 50 yards (46 m) down the side of CD-22, raked her with 20 mm gunfire and her deck gun.

Salmon began sending out plain language directions for all other subs in the vicinity to attack, giving the position of the action.

On 10 November, Salmon stood out from Saipan, in company with Holland, and sailed via Eniwetok and Pearl Harbor to San Francisco.

On 26 January 1945, she departed from San Francisco with the submarine Redfish and proceeded via the Panama Canal to Portsmouth, New Hampshire, where she arrived on 17 February.

Salmon was awarded the Presidential Unit Citation for extraordinary heroism against enemy surface vessels during her eleventh war patrol in restricted, enemy-held waters of the Pacific.