Besugo put to sea from Pearl Harbor for her first war patrol on 26 September 1944, escorted until dark by the submarine chaser USS PC-486.

In company with the submarine USS Gabilan (SS-252), Besugo headed west and stopped at Midway Atoll in the Northwestern Hawaiian Islands to refuel on 30 September.

Unable to return fire effectively, Besugo withdrew, leading her commanding officer to remark, "Not an auspicious beginning to our fighting career."

On 8 October 1944, Besugo spotted an Imperial Japanese Navy Mitsubishi G4M Type 1 bomber (Allied reporting name "Betty") and submerged for the remainder of the day.

Owing to the upcoming U.S. landings on Leyte in the Philippine Islands, scheduled for 20 October, Besugo had orders to spot any Japanese heavy fleet units departing the Bungo Channel and to refrain from firing at any targets until after sending in a contact report.

On 18 October 1944, Besugo spotted two more warships, this time entering the Bungo Channel rather than leaving it, and noted the contacts in accordance with her orders.

Following minor repairs and a torpedo reload, Besugo departed Tanapag Harbor at Saipan to begin her second war patrol on 10 November 1944.

Returning to her patrol station that evening, Besugo encountered rough weather, and the heavy swells interfered with her surface search radar.

Two of them demolished the midships section and the ship settled to the bottom in 6 fathoms (36 ft; 11 m) of water, leaving the superstructure still visible above the surface.

With her torpedoes gone, Besugo headed south, passed through the Lombok Strait, and arrived at Fremantle, Australia, on 4 December 1944, bringing her patrol to an end.

At 18:40 on 6 January, her lookouts sighted the heavily laden Japanese 10,020-gross register ton tanker Nichei Maru escorted by a destroyer and two coast defense frigates.

Twenty minutes later, Besugo tried approaching again and, despite sonar searches and a close depth-charge attack by the escorts, she fired six torpedoes at the tanker.

A week later, Besugo discovered four Japanese antisubmarine warfare vessels conducting a sound sweep off Cape Laguan on the Malay Peninsula.

Passing through Lombok Strait on 31 March, she joined the submarines Gabilan and USS Charr (SS-328) and took up a position near Bangka Island off Sumatra on 3 April 1945.

Later on the morning of 5 April 1945, Besugo received orders to patrol the Sumba Strait while Allied aircraft from Australia attempted to sink the elusive Japanese task group.

Besugo spent the next two hours dodging Japanese air attacks; she was bombed once and strafed twice, before finally sinking W.12′s stern section with her last torpedo.

On the evening of 29 April, after closing with an immense pillar of fire spotted over the horizon, Besugo rescued a badly burned sailor, most likely from the Imperial Japanese Army tanker Yuno Maru, recently sunk by a mine.

After transiting Lombok Strait, she arrived at Fremantle on 25 July 1945 and received a refit alongside the submarine tender USS Clytie (AS-26).

One training measure, devised to give submarine crews experience was the "simulated war patrol," a mission upon which Besugo embarked on 7 June 1947.

After exchanging information with Diodon, Besugo moved to St. Lawrence Island on 19 July and began three weeks of photo reconnaissance operations off Cape Navarin on the coast of the Soviet Union at the southern extremity of the Gulf of Anadyr.

After a rendezvous with the submarine Blower on 10 August 1948, Besugo proceeded to Adak and Kodiak, Alaska, before returning to Pearl Harbor on 20 July 1948.

She remained in Hawaiian waters for the next 18 months, conducting independent ship's drills, antisubmarine warfare exercises, and other local operations from Pearl Harbor.

After four weeks of training, including target services for U.S. antisubmarine warfare planes and warships, she began the first of her two Korean War reconnaissance patrols.

During her first visit to Okinawa, she proceeded to Naze Ko on Omami o Shima on 12 January 1951 to rescue six survivors of a PBM Mariner flying boat that had crashed.

Following nine months of local operations in Hawaiian waters and two shipyard periods, during which new sonar equipment and mine clearing cables were installed, Besugo got underway from Pearl Harbor on 7 January 1952 bound for Subic Bay in the Philippines.

Besugo returned to Subic Bay on 28 February 1952, and then to Pearl Harbor in March 1952, after which Besugo′s crew received a two-month leave and upkeep period.

She returned to Pearl Harbor on 29 March 1953, and her only other movement later in the spring of 1953 was a mid-May visit in Hawaiian waters to Nawiliwili Bay on Kauai.

Her first training cruise took place in the autumn of 1954, when she proceeded from San Diego to Lahaina Roads in Hawaii and laid a drill minefield on 21 October 1954.

In the autumn of 1955, Besugo visited the Puget Sound area again for antisubmarine warfare exercises with Royal Canadian Navy warships and a U.S.

In January 1957, in company with the submarine USS Remora (SS-487), she made a cruise sto Mexico which included a port visit at Mazatlan.