After shakedown off the United States East Coast and further training in Hawaiian waters, Queenfish set out on her first patrol 4 August 1944, in Luzon Strait.

Tunny had to withdraw after being damaged by air attack, but on 31 August, Queenfish made her first kill, the 4,700-ton tanker Chiyoda Maru.

Alerted by ComSubPac to the approach of a large convoy from Manchuria carrying reinforcements for the Philippines, the "Loopers" and another wolfpack, the "Urchins", combined to attack.

The ship had been guaranteed safe passage by the United States government, since she was to carry Red Cross relief supplies to Japanese POW camps.

After overhaul at Mare Island Naval Shipyard, Queenfish assumed duties as flagship, Submarine Force, Pacific Fleet.

Homeported at Pearl Harbor after the war, Queenfish returned to the Far East during March 1946 and in June–July 1949, but spent most of the period to 1950 in training operations in the eastern Pacific.

The next four years were spent operating off the west coast of the United States, with the exception of two weeks in Hawaii in late 1956.

On 16 January 1958 she departed for a six-month deployment to WestPac, returning to San Diego 27 July to resume operations off the west coast of the United States.

Queenfish was awarded the Presidential Unit Citation, and received six battle stars for World War II service.