She was laid down on 1 November 1939 by the Boston Navy Yard, launched on 31 May 1940; sponsored by Mrs. Bessie Wilkes Styer; and commissioned on 22 April 1941.

The destroyer arrived in Bermuda on 24 August and helped to screen the battleships North Carolina and Washington on their shakedown cruises in the Caribbean.

During the destroyer's passage to Iceland, Japanese naval aircraft attacked the Pacific Fleet's base at Pearl Harbor, pushing the United States into full participation in World War II.

On 5 January, Wilkes departed Casco Bay in company with Madison, Roper, and Sturtevant, bound for Naval Station Argentia, Newfoundland.

While en route to Argentia, Newfoundland, at about 03:50 on 18 February 1942, Wilkes's commanding officer was awakened by the navigator and informed that the ship was believed to be northward of the plotted track.

[1] On 1 April 1942, Wilkes was assigned to Task Force 21 (TF 21) at the Boston Navy Yard where she conducted post repair trials and underwent a three-day availability.

One minute later, the two ships collided — Davila's bow struck Wilkes on the port side abreast of her number one fireroom.

After the two ships separated, the destroyer returned to Boston where she entered the navy yard for restricted availability which continued until 3 June.

Following gunnery and antiaircraft practice and antisubmarine exercises at Casco Bay, Wilkes made a short escort mission screening Convoy BX-26.

On 1 July 1942, the destroyer sailed for Little Placentia Harbor, Newfoundland, where she performed escort and patrol duty before returning to New York where she remained until the 12th.

Large amounts of air were seen to emerge at the scene of the attack in the center of which appeared the bow of a submarine, which then rolled over and disappeared, apparently out of control.

Three days later, Wilkes was detached from the formation and proceeded to Trinidad, where she refueled before sailing for the Virginia capes and arrived at Norfolk on 25 July.

The ship made radar contact on the surface, and a short while later her fire control party reported a dark object in the water.

However, the shore battery on Pointe d'Oukach opened fire, and Wilkes was forced to discontinue her chase as the destroyer retreated back to Casablanca.

On 11 November, Wilkes received news that Casablanca had capitulated; and the destroyer then resumed patrolling the area around the convoy anchorage.

Bristol illuminated to open fire on a surfaced submarine and also made a depth charge attack with negative results.

She spent the month of December conducting short escort and patrol missions in waters in New York and Casco Bay, Maine.

Wilkes began the new year 1943 with two voyages from New York to Casablanca and back, taking place between 14 January and 14 February and between 6 March and 5 April.

Two days later, she embarked American Army troops, complete with equipment, and got underway with eight other destroyers and three high-speed transports and sailed for Los Negros Island of the Admiralty group in order to reinforce elements of the 1st Cavalry Division who were then holding the beachhead.

The destroyer remained there to operate as a fire support ship and received on board casualties evacuated from the combat areas.

The next day, Wilkes bombarded Lemondrol Creek, just south of Momote air strip, and targets on the western end of Hayne Harbor.

She continued performing such duty through 7 March when Wilkes proceeded to Seeadler Harbor, at Manus Island, Admiralty Group, to assist in the landings there.

On 9 April, she steamed back to Seeadler Harbor to escort a convoy from Los Negros Island to LanFemak Bay, New Guinea.

On 22 April 1944, the destroyer participated in the landings at Tanahmerah Bay, New Guinea, and, after the troops had gone ashore, continued operations in that area.

The destroyer then continued operations in the Humboldt Bay area and spent the latter part of June bombarding targets ashore on Aitape and Toem, New Guinea.

On 28 January 1945 after completing her availability and post-repair trials Wilkes made rendezvous with the aircraft carrier Franklin and proceeded to San Francisco.

They departed the following day and, after making mail deliveries, Wilkes returned to her patrol station covering the carrier strikes on Nansei Shoto.

Five days later, Wilkes was anchored at Ulithi Atoll, Caroline Islands, undergoing voyage repairs and routine upkeep.

On 24 August, Wilkes got underway as part of the autosubmarine screen with Task Unit 30.8.9 (TU 30.8.9) patrolling off the Mariana and Bonin Islands.

Wilkes departed the west coast on 16 November transited the Panama Canal, and reached Charleston, South Carolina, on 2 December.