Following shakedown off Bermuda, Picking proceeded via the Panama Canal to Dutch Harbor, Alaska, where she arrived 28 December 1943 to serve with the North Pacific Fleet, Destroyer Squadron 49.

In August she steamed to San Francisco, California for upkeep, and then to Hawaii, arriving Pearl Harbor on the 31st where she joined the 3rd Fleet.

Following replenishment at Manus, Picking provided antiaircraft protection for the beachhead at Lingayen Gulf, Philippines on 9 January 1945.

Following replenishment at Leyte, the destroyer arrived off Kerama Retto, Ryukyus on 26 March, and screened transports during landings that morning.

Upon completion of Korean duty, she departed Sasebo, Japan on 5 August, and proceeded via the Suez Canal to Boston arriving 2 October.

Operating out of Derry, Northern Ireland, she studied British convoy escort techniques, and then served with the 6th Fleet, before returning to Newport 26 May.

She departed 5 June for a tour of duty with the 7th Fleet, which included a Taiwan patrol, and returned to Long Beach 18 November.

On her next WestPac deployment, 8 October 1958 to 27 March 1959, she operated with an antisubmarine hunter-killer group led by the aircraft carrier Yorktown.

Deployed to the 7th Fleet on 13 March 1964, she performed escort duty off Vietnam in response to the Gulf of Tonkin incident before returning to Long Beach 2 October.

Following gunfire support duty off South Vietnam and a return to Yankee Station, she arrived Long Beach 17 August.