Following shakedown off California and extended exercises in Hawaiian waters, Preston departed Pearl Harbor, for the Marianas combat zone, 1 July 1944.

Between 6 and 8 September, she screened the aircraft carriers during strikes against the Palaus; then, continuing on, guarded them during sorties against Japanese positions in the south and central Philippines.

On completing runs on the 14th, she returned with the force to the Palaus to cover the landings on Peleliu and Anguar, then sailed back to the Philippines before retiring to Ulithi.

After hitting the enemy's Formosan air bases, the force turned southeast for operations off Luzon in support of the Leyte landings.

On 30 December the force again steamed northwest from Ulithi, and after welcoming the new year, 1945, with raids on Formosa and the Nansei Shoto, supported the Lingayen assault.

During February, Preston screened the carriers as their planes delivered devastating blows to industrial complexes on the Japanese home islands; provided air support for the assault troops on Iwo Jima; returned to Japan for further strikes on Tokyo, Nagoya, Osaka, and Kobe; and then sailed south for renewed raids against the next amphibious target, Okinawa.

In July, she patrolled off northern Okinawa on radar picket duty and, in August, escorted convoys in and out of the Buckner Bay area.

With the signing of the truce 27 July, Preston got underway for Newport and, steaming via Suez, completed the round-the-world cruise, at Boston, in October.

In 1955 another Mediterranean deployment was followed by antisubmarine warfare (ASW) exercises and on 15 March 1956, she cleared Narragansett Bay and headed back to the west coast.

Assigned to Destroyer Squadron 23 (DesRon 23), Preston arrived at Long Beach 15 April and through May operated off the California coast.

In June, she sailed west for her first peacetime Far East deployment and initiated a schedule of regular rotation between tours with the 7th Fleet in the western Pacific and 1st Fleet assignments; the former including SEATO and other Allied exercises and Taiwan patrol duty, and the latter including west coast training and cruises to the Arctic and to the central Pacific.

Joining TG 77.5 on 12 August, she performed plane guard and screening duties for the carriers Coral Sea (CV-43) and Ticonderoga (CV-14), and provided gunfire support to ground troops until late 1968.