After transiting the Panama Canal in mid-November, the submarine reached Pearl Harbor early in December and conducted intensive training in preparation for her first war patrol.
On 30 January, Threadfin sighted a large enemy patrol craft, but prudently allowed her to pass unmolested in the hope of drawing a bead on any merchant vessels for which she might be running interference.
The cargoman probably sank; but Threadfin could not verify that result visually because the escorts drove her deep with a persistent, though ineffective, depth charge attack.
The following day, she mistook another patrol vessel for a cargo ship and discovered her mistake in just enough time to make a deep dive to safety.
The stricken warship's screws stopped while her colleague's depth charge attack deprived Threadfin of definite knowledge of the ultimate result.
On 31 March, that group was dissolved, and Threadfin received orders to join Hackleback and Silversides near Bungo Suido, the primary entrance to the Seto Inland Sea which separates Honshū from Kyūshū and Shikoku.
The new attack group's primary assignment was to guard against an undetected sortie of the remainder of Japan's fleet during the Allied assault on Okinawa.
On the evening of 6 April, Threadfin made radar contact with what later proved to be an enemy task force built around Japan's super battleship, Yamato.
Passing up a tempting opportunity in order to carry out her prime directive, Threadfin flashed the warning to Fifth Fleet headquarters afloat off Okinawa.
The next day, the submarine encountered a freighter sunk in shallow water and surrounded by small boats, apparently conducting some variety of salvage operations.
She fired a single torpedo which caused the wreck to settle a further ten feet and which she hoped would suspend the suspected salvage operations.
On the return trip from her final war patrol, Threadfin rescued three survivors from a downed American flying boat and took them to Guam where she arrived on 27 July.
That duty apparently lasted until December 1952, at which time the submarine was decommissioned to enter the Portsmouth Naval Shipyard for an extended conversion overhaul.
Finally, her underwater performance was boosted by the installation of two "greater capacity" batteries—they actually produced the same power as the old style batteries but in a smaller, lighter physical plant—and a snorkel for extended submerged cruising.
In October, she conducted her post-conversion shakedown cruise and, early the following month, reported for duty as a unit of Submarine Squadron 4 at Key West, Florida.
She participated in several exercises each year and frequently conducted summer training cruises for United States Naval Academy and NROTC midshipmen.
Though based in Key West, she made visits to ports on the Gulf of Mexico such as New Orleans, Louisiana, and often ventured north to New London, Connecticut.
The following summer, the submarine made what, on the basis of sparse records, appears to be her only post-war overseas deployment with the Sixth Fleet in the Mediterranean Sea.
After successive years of routine operations in the Caribbean Sea and Atlantic Ocean, Threadfin was placed out of commission on 18 August 1972 and transferred to Turkey that same day.