Heywood L. Edwards conducted her shakedown beginning 25 February off Bermuda and after gunnery exercises off the Maine coast departed to join the Pacific Fleet.

Sailing from Boston, Massachusetts on 16 April, she transited the Panama Canal, stopped at San Diego, California and arrived at Pearl Harbor on 8 May.

The ships got underway from Pearl Harbor on 29 May for the Marianas with Heywood L. Edwards acting as screening unit for the transport group and during the initial landings on Saipan on 15 June the destroyer took up patrol station to seaward of the invasion beaches.

Heywood L. Edwards took part in the Peleliu operation, departing 18 August for training exercises with amphibious forces on Florida Island and sailing for the western Carolines 6 September.

There she joined with Rear Admiral Jesse B. Oldendorf's fire support and bombardment group for the return to the Philippines, departing for Leyte 12 October 1944.

As Oldendorf's deployed forces waited at the end of Surigao Strait, Heywood L. Edwards headed section 3 of Destroyer Squadron 56 (DesRon 56), screening the left flank of the cruiser line.

With the Allied victory complete at sea, Heywood L. Edwards remained in the invasion area until 25 November, patrolling and protecting the shipping building up in the gulf.

TF 54 departed Ulithi on 21 March and after her arrival 4 days later Heywood L. Edwards covered the UDT teams' reconnaissance of Kerama Retto.

She covered the UDT landings on Okinawa on 30 March, shelled an airfield ashore that afternoon and on 1 April joined in the bombardment of the assault areas.

Sailing toward Japan, Heywood L. Edwards covered the initial occupation of the Ominato area on 6 September 1945 and departed that port on 22 October for the United States, via Pearl Harbor.

Heywood L. Edwards received seven battle stars for her service in World War II and a Navy Unit Commendation for her outstanding part in the great amphibious operations of 1944–45.