After shakedown training out of Guantanamo Bay, the new destroyer steamed north for post-shakedown availability and voyage repairs in the Boston Navy Yard.

Reaching Pearl Harbor on 9 August, Wadsworth spent 10 days in the Hawaiian operating area before heading for Canton Island in the screen for the carrier Prince William.

Subsequently, touching Espiritu Santo, in the New Hebrides Islands, Wadsworth reported to Rear Admiral Aubrey W. Fitch, Commander, Aircraft, South Pacific (ComAirSoPac), for duty.

On the last day of August 1943, Wadsworth cleared Espiritu Santo to hunt for the Japanese submarine—later identified as I-20—that had torpedoed and damaged the tanker W. S. Rheem about 10 miles (16 km) north of Bougainville Strait.

Wadsworth made no contact with any submarines in the first area searched but then teamed with amphibious patrol planes to scour the seas to the south of Espiritu Santo and west of Malakula Island.

Returning to Efate with empty cargo ships on 30 September, Wadsworth took a screening station near the battleship South Dakota to escort her to the west for a rendezvous with a cruiser-battleship striking force under the command of Rear Admiral Willis A. Lee.

Wadsworth subsequently joined other units of Destroyer Division 45 (DesDiv 45) as part of the protective screen for a dozen troop transports, Task Group 31.5 (TG 31.5), bound for the Solomons and the initial landings of men in Empress Augusta Bay, Cape Torokina, Bougainville.

On this occasion, Wadsworth took a fighter-director station off the transport area and assisted in repelling a noon enemy air attack, her guns claiming one dive bomber and one torpedo plane.

Wadsworth operated in support of the Bougainville occupation through the end of 1944, escorting troop-and supply-laden convoys from Kukum beach, Guadalcanal, to Empress Augusta Bay.

Three days after Christmas 1943, she blasted Japanese trenches and gun emplacements on both the south and north sides of the mouth of the Reini River, aided by air spot.

Subsequently, taking on ammunition at Hawthorne Sound, New Georgia, Wadsworth left on the night of 1 February to exercise with motor torpedo boats off Rendova.

Near midnight, she helped to repel enemy air attacks on the Torokina beaches, before she left the area the next morning, screening the tanker Patapsco to Purvis Bay.

Before dawn on 15 February, Wadsworth, acting as fighter-director ship, vectored night fighters toward an enemy raid of five planes that dropped flares off the formation.

After putting into Purvis Bay on the night of 17 February, Wadsworth steamed to Kukum beach and joined a troop convoy earmarked for the Green Island occupation.

A few minutes after midnight on 24 February, the destroyer opened fire and shelled a supply dump, stowage houses, and enemy troop concentrations in that area.

With Purvis Bay as her base of operations, Wadsworth escorted supply convoys to Green Island and from Guadalcanal to Cape Torokina until 17 March.

Assigned to duty with Battleship Division 3 (BatDiv 3)—comprising Idaho, New Mexico, and Pennsylvania—Wadsworth engaged in battle maneuvers and training off the New Hebrides in preparation for the conquest of the Marianas.

However, the respite provided by that in-port period was brief, for Wadsworth proceeded to sea on 17 July, as part of the escort for troop-laden transports slated to put their combat-garbed marines and soldiers ashore on Guam.

Wadsworth patrolled off that isle as those men splashed ashore and, while engaged in that duty 26 miles (42 km) offshore, picked up eight natives of Guam, who had escaped from the Japanese, on the morning of 22 July.

Relieved by the destroyer Hudson on 2 August, Wadsworth then spent four days acting as primary fighter-director ship off Agana beach for two divisions of fighters based on the carriers Belleau Wood, Langley, and Essex.

Proceeding via Eniwetok, Ulithi, and Pearl Harbor, the destroyer arrived at the Mare Island Navy Yard on 25 October for a major overhaul and completed that period of repairs and alterations on 5 December.

Reaching the Palaus on 16 January, Wadsworth relieved the destroyer Lansdowne as tender for four minesweepers and two subchasers (SCs) engaged in patrols between Peleliu and Angaur Islands.

In the early morning darkness two days later, she illuminated a target heading for the transport area and received information that there were no friendly small craft in the vicinity.

The next morning, Wadsworth took station in the fire support sector off Iwo Jima and blasted enemy tanks and mortar and rocket positions.

She continued that action in support of the ground troops ashore until the afternoon of the 21st, when she resumed screening duty for transports carrying the occupation force which ultimately landed on 2 March.

His wing struck the forward port 40-millimeter gun, and the main body of the plane spun into the gig rigged outboard, carried away a life raft, and then smashed a 26-foot (7.9 m) motor whaleboat before falling into the sea.

Since her first arrival off Okinawa, she had sounded general quarters 203 times, detected and reported the approach of hundreds of enemy aircraft, and successfully fought off all that attacked her.

After "V-J Day" in mid-August, Wadsworth remained in the Far Eastern area, clearing Okinawa on 12 September, bound for Nagasaki, Japan, as escort for two LSTs.

Soon thereafter, she commenced transport and occupation duties, carrying troops and escorting their vital supply ships between Sasebo, Wakayama, and Yokosuka—duties in which she remained engaged through mid-November.

Sailing via the Hawaiian Islands, the destroyer reached San Diego between 6 and 10 December and disembarked returning veterans at that port before she headed on for Panama.