On 10 January 1943 during its third war patrol in the Southwest Pacific, Argonaut sighted an Imperial Japanese Navy convoy protected by planes and destroyers.

Following her shakedown cruise off Bermuda, John R. Pierce operated out of Norfolk, Virginia during the spring of 1945, where she trained destroyer crews and conducted antisubmarine warfare (ASW) patrols along the eastern seaboard.

She sailed on 21 December from Kure, Honshū, to Shanghai, China, to support the Chinese Nationalists in their conflict with the Communists for control of the mainland.

Arriving on 5 August, she commenced twelve months of Atlantic operations that extended from Greenland to the Panama Canal Zone.

Before she returned to the United States on 23 January 1951, she operated in the Mediterranean from Gibraltar to Crete and along the western coast of Europe from England to Norway.

When in the Mediterranean, fleet operations carried her the length and breadth of the sea, and deployments in 1954 and 1956 sent her, in addition, to the coast of Western Europe.

Engaged primarily in conducting ASW barrier patrols and screening carrier flight operations, John R. Pierce responded when the Syrian Army threatened King Hussein's pro-Western government of Jordan during August and September 1957, destroyers, including John r. Pierce, patrolled the sea lanes of the Eastern Mediterranean and the Red Sea to guard against possible intervention by Egypt.

She returned to the same area in December 1958 to bolster the security of Lebanon, recently threatened by the Soviet-backed United Arab Republic.

Returning to Norfolk 1 April 1962 from her seventh Mediterranean cruise, she sailed on 15 May to participate in Project Mercury recovery operations following Lieutenant Commander M. Scott Carpenter's scheduled three-orbit flight in Aurora 7.

On 24 April she steamed 206 miles at flank speed from her designated position in the Atlantic Recovery Area east of Puerto Rico and recovered the floating space capsule.

After delivering it safely at Roosevelt Roads, Puerto Rico, the next day, she returned to Norfolk 28 May before resuming duty in the Caribbean.

John R. Pierce departed from her assigned position the following day, but she continued a Caribbean sea-vigil from Jamaica to the Canal Zone until returning to Norfolk 14 December.

John R. Pierce spent the next year operating out of Norfolk; and during off-shore surveillance patrols in January 1964 she escorted five Cuban boats, which were illegally fishing in U.S. territorial waters, to Key West for internment.