The ship was named in honor of the five Sullivan brothers (George, Francis, Joseph, Madison, and Albert) aged 20 to 27 who died when the light cruiser, USS Juneau, was sunk by a Japanese submarine during the Naval Battle of Guadalcanal on 13 November 1942.

Thereafter, the destroyer continued her operations to the north and northwest of Roi and Namur Islands throughout the Battle of Kwajalein until 4 February, when TG 58.2 retired to Majuro to refuel and replenish.

After returning to Majuro for replenishment, the warship screened TG 58.2 during air strikes on Hollandia (currently known as Jayapura), Tanahmerah, Wakde, and Aitape to support amphibious operations on New Guinea.

American air attacks against Pagan Island, made without enemy retaliation, topped off the Saipan-Tinian-Guam strikes; and The Sullivans proceeded with TG 58.2 to Eniwetok for upkeep.

The heavy ships in the group opened fire at 15:00, and smoke and dust soon obscured targets along the western shore of the island, making spotting difficult.

From 7 to 22 July, TG 58.2 operated south and west of the Marianas, conducting daily air strikes on Guam and Rota Islands before returning to Garapan Anchorage, Saipan, to allow the carriers to replenish bombs.

Meanwhile, The Sullivans and the other ships in formation executed 38 simultaneous turn movements at speeds between 22 and 25 knots (46 km/h; 29 mph) as their guns kept up a steady fire to repel the attackers.

At dawn of the 24th, reconnaissance located a Japanese surface force south of Mindoro, and the American carriers launched air strikes all day against the enemy warships.

At dusk on the 19th, during one of the many air attacks fought off by The Sullivans, the destroyer damaged a "Betty" by gunfire and watched it disappear over the horizon, smoking but stubbornly remaining airborne.

The Sullivans, her "lucky shamrock" painted on her funnel, emerged from the typhoon undamaged and, on the 20th began searching for men lost overboard from other ships.

After a brief run to Manus and back, escorting Iowa, The Sullivans sortied from Ulithi on 30 December to screen TG 38.2's air strikes on Formosa in support of the American landings on Luzon.

During subsequent air strikes on Hainan Island, Hong Kong, and Formosa, The Sullivans served on radar picket duty 10 miles (16 km) ahead of the task group.

A brief respite for upkeep at Ulithi in late January preceded the ship's deployment with TG 58.2, covering the carriers as they launched devastating air strikes against the Japanese homeland itself, hitting Tokyo and other targets on Honshū on 16 and 17 February.

The stricken destroyer lost steering control and started to veer across the big carrier's bow, and only rapid and radical maneuvering on Hancock's part averted a collision.

She slowed to a stop 11 minutes later and lowered her motor whaleboat to transfer her medical officer and a pharmacist's mate to Halsey Powell, when another kamikaze came out of the skies, apparently bent on crashing into The Sullivans.

At 16:10, the destroyer's radar picked up the "Zeke" on its approach; and, as soon as the motor whaler was clear of the water, The Sullivans leapt ahead with all engines thrusting at flank speed.

Bringing right full rudder, The Sullivans maneuvered radically while her 20- and 40-millimeter guns sent streams of shells at the "Zeke", which passed 100 feet (30 m) over the masthead and escaped.

On the afternoon of 29 April, she commenced fueling from Bunker Hill, but a kamikaze alert interrupted the replenishment, forcing The Sullivans to break away from the carrier's side.

The Sullivans promptly closed the carrier to render assistance and picked up 166 men forced over the side by the fires that at one point ravaged the ship.

Meanwhile, since the return of peace greatly reduced the Navy's need for warships, The Sullivans was decommissioned at San Diego on 10 January 1946—soon after her overhaul was completed—and she was placed in the Pacific Reserve Fleet.

She supported the carriers as they made the northernmost stab at North Korean supply lines, approaching within 75 miles (120 km) of the Soviet base at Vladivostok, Russia.

Arriving in Area "G" the following day, The Sullivans made contact with the enemy on the 16th off Songjin, North Korea which was an important rail terminus and supply center.

After their presence had dispelled the crisis, she returned to the United States for a three-month navy yard overhaul and subsequent refresher training at Naval Station Guantanamo Bay, Cuba.

Then, after making a midshipman training cruise for USNA and NROTC midshipmen in which she also conducted antisubmarine warfare operations, the destroyer sailed for another Mediterranean deployment which lasted until she returned home in the autumn.

During this deployment to southern climes, on 31 March and 1 April, the warship helped to rescue five of eleven survivors from a U.S. Air Force KC-97 Stratofreighter(Model F Stratotanker) that had ditched 40 miles off the Florida coast near Cape Canaveral.

Following NATO exercises in September, The Sullivans visited Lisbon, Portugal, prior to a quick trip through the Mediterranean, Suez Canal, and Red Sea, to Karachi, West Pakistan.

In January 1961, The Sullivans assisted in the sea trials of the nuclear-powered fleet ballistic missile submarine Abraham Lincoln off Portsmouth, New Hampshire, before steaming south and taking part in Operation Springboard.

Briefly back at Newport early in March, The Sullivans soon returned to the West Indies to support marine landing exercises at Vieques, Puerto Rico.

On 5 May 1961, Commander Alan Shepard's Mercury space capsule, Freedom 7, passed overhead and splashed down near Lake Champlain and was speedily rescued by helicopters from the carrier.

Her cruises with the reserves embarked were devoted mostly to ASW exercises and took the ship to Canadian ports such as Halifax, Nova Scotia; Saint John, New Brunswick; and Charlottetown, Prince Edward Island, in the north; and to Palm Beach, Florida, in the south.