After shakedown in the Caribbean, Murray served on escort duty in the Atlantic Ocean, then sailed to join Destroyer Squadron 25 at Pearl Harbor in September 1943.

Sailing with a carrier task force, Murray took part in strikes on Wake Island 5–6 October, then voyaged to the South Pacific to support the landings on Bougainville 8–9 November, splashing three enemy aircraft.

In January 1944 Murray performed outstandingly in fire support missions for the capture of Kwajalein, then screened transports carrying invasion forces to Eniwetok.

Joining the 7th Fleet Murray took part in the assault on Aitape, New Guinea, 23 to 28 April, downing another enemy aircraft during an aerial torpedo attack.

Departing the Philippines immediately after the landings Murray overhauled at San Francisco, California, then in January 1945 escorted a battleship division to Pearl Harbor while en route to join Task Force 58.

One of the initial occupation force, Murray became the first ship in empire waters to bring in a Japanese submarine when the enemy undersea fleet began to surrender.

On 27 August, aircraft of TF 38, patrolling off Honshū, located a submarine flying the black flag designated as the surrender signal, and Murray was ordered to intercept and take the craft into Tokyo Bay for internment.

During much of 1956 she underwent yard overhaul, then in 1957 sailed round Cape of Good Hope for patrol duty in the Persian Gulf, the usual access to which was blocked by the closing of the Suez Canal the previous autumn.

In late May 1961, Murray was one of the rescue ships stationed along the route of President John F. Kennedy's flight to Paris, then participated in that summer's midshipmen cruise.

Redesignated DD-576 on 30 June 1962, Murray rejoined TG Alfa for its development operations, which were interrupted for participation in the Cuban Quarantine in October and November 1962 that forced Soviet missiles out of Cuba and averted grave international complications.