Laid down on 27 May 1944 at Bath Iron Works, Bath, Maine; Southerland was, after her sister Frank Knox, the second Gearing commissioned and one of only two to join the fleet in 1944, Comdr. Russell C. Williams in command.

After shakedown and exercises in the Alantic, she departed for the Pacific on 24 April 1945 and arrived at Pearl Harbor on 15 May. She operated from Ulithi and then Leyte, from which she stood out on 1 July with the fast carriers of Task Force 38 for air strikes on the Japanese home islands, 10 July–15 August, with bombardment missions on 29–30 July and 9–10 August.

On 27 August 1945, Southerland anchored with the Third Fleet in Sagami Wan. On the 28th, she led the first column of Allied ships into Tokyo Bay to occupy the Yokosuka Naval Base and thus commenced four months of occupation duty.

Returning to San Diego in January 1946, Southerland was demobilized but returned to the Central Pacific in November, thus beginning a pair of cruises to China and Japan through February 1949. Redesignated DDR 743 on 18 March 1949, she was in Hawaii in June 1950, when the Korean War broke out. There followed eight tours off Korea through 1953, during which she bombarded targets ashore and supported the landings at Inchon, 15 September but sailed for the West Coast after sustaining damage from counterbattery fire on the 16th.

A year later, on 10 February 1952, Southerland was back off Japan. On the 14th, she joined TF 95, the United Nations Blockade and Escort Force, off the west coast of Korea. Carrier escort and coastal patrol duty followed, involving night shore bombardment against enemy transport facilities, boat and troop concentrations and gun emplacements.

In March, the destroyer conducted ASW exercises off Okinawa; and, in April, as the stalemate in the Panmunjom armistice negotiations continued, she returned to the combat zone. Joining TF 77, she screened carriers, served as plane guard and participated in shore bombardments-including a combined air/sea strike on Ch’ongjin on Easter Sunday.

On 18 April, Southerland returned to Yokosuka; then steamed to Okinawa for ASW operations. On 11 May, she rejoined TF 77 and, for 28 days, supported the carriers as they struck targets at Ch’ongjin, Wonsan and other areas. In June, her carrier group shifted to targets inland.

Toward the end of the month, as interservice air strikes hit Communist power sources, Southerland again headed south for Taiwan Strait patrol duty. On 10 July, she rejoined TF 95 off the Korean east coast; and, on the 14th, engaged in a 23-minute duel with seven shore batteries. Taking four direct hits, with eight minor casualties, she made temporary repairs at sea; then continued her patrol. On the 22d, she put into Sasebo; and, on 10 August, she arrived back in her homeport, San Diego.

Seven months later, the ship departed San Diego for her third combat tour off Korea. From mid-April to mid-May and again in June, she patrolled off the Korean coast. On the 27th, she returned to Japan; and, one month later, was assigned to patrol duty along the truce line. On 2 October, she sailed for home.

After Korea, Southerland alternated duty with the Seventh Fleet in the western Pacific (WestPac) with training assignments, 1st Fleet operations and upkeep and overhaul periods. Her Far East deployments included SEATO exercises; Taiwan Strait patrols; Seventh Fleet exercises; and, during her 1957 and 1958 WestPac tour, relief work. At the end of December 1957, she joined Princeton (CVS 37) and Henderson (DD 785) in providing emergency relief—food, medicine and trained medical personnel—for survivors of devastating floods in Ceylon; and she continued that work into January 1958.

In the eastern Pacific, she conducted training exercises, participated in First Fleet exercises; and, in 1962, joined Joint Task Force 8 for operation “Dominic,” the upper atmosphere nuclear test series at Christmas Island.

In November of 1963, Southerland, in WestPac and scheduled to participate in amphibious support exercises, was ordered to Vietnam for brief duty as hostilities there threatened American interests. Soon departing, she returned to California for a 10-month FRAM, Mark I, overhaul and conversion at Mare Island. During that period, her superstructure above the main deck was removed; berthing and messing areas were renovated; and her engineering spaces were reconditioned. Electronically modernized, her ASW capability was enhanced by the addition of ASROC, an antisubmarine rocket system.

Work was completed in October 1964. Southerland, redesignated DD 743 on 1 April 1964, then tested her new equipment and conducted training exercises until March 1965. She next headed west to return to Vietnam and her third war in the western Pacific.

Departing on 6 March, she joined TF 77 in the South China Sea; and, as in Korea, she screened carriers and acted as plane guard while strikes were flown against Communist targets. After duty with TF 77, she shifted to operation “Market Time,” for trawler surveillance duty. Briefly detached twice in late June, she provided gunfire support in the I Corps area and destroyed several Viet Cong buildings and communications points.

On 11 September, Southerland arrived back at San Diego. Nine months later, she was underway for another combat tour off Vietnam. On 8 July 1966, she arrived off the embattled coast and, for 11 days, operated with Intrepid (CVS-11) near the Mekong Delta. Detached on the 19th for fire support duty, she returned to the carrier on the 28th; and, at the end of the month, retired to Subic Bay. On 7 August, she was again off Vietnam. Until the end of the month, she operated in Tonkin Gulf with Franklin D. Roosevelt (CVA-42). ASW exercises followed; and, in mid-September, she sailed for Japan. At the end of October, she returned to Tonkin Gulf for search and rescue duty.

On 23 November, Southerland completed her Vietnam tour and headed home. In February 1967, she served as ASW School Ship and, in March, as Engineering School Ship. From April to August, she underwent overhaul. In the fall, she conducted refresher training; and, on 28 December, she sailed for WestPac and another tour off Vietnam.

From then until 28 June 1968 and again from 18 March to 3 July 1969, Southerland operated with the Seventh Fleet on assignments similar to those in 1965 and 1966. In 1970, she sailed west in mid-June; operated in Japanese waters through the end of July; then steamed south, for Vietnam, on 6 August. There, she again alternated carrier escort and plane guard duties in Tonkin Gulf with fire support activities off the southern coast of the divided country until mid-November. On 1 December, she returned to San Diego.

During the first half of 1971, Southerland spent two periods underway, one in January and one in April. Both were in conjunction with Composite Unit Training Exercises conducted in the southern California (SOCAL) operating area. On 29 June, she got underway from San Diego en route to the western Pacific. She remained in the Far East until 5 December, plane guarding for Enterprise (CVAN-65) and visiting such oriental ports as Hong Kong, Singapore and Subic Bay. After a 17-day passage, Southerland returned to San Diego on 22 December.

On 2 June, the ship entered the Long Beach Naval Shipyard and commenced an overhaul which lasted until 9 November. During the yard work, her main propulsion plant was converted to use navy distillate fuel.

The destroyer continued her operations out of San Diego along the southern California coast until mid-June 1973. On the 11th, she stood out of San Diego and headed north to Seattle, Wash. There, she embarked naval reservists and shaped a course for the western Pacific, via Adak, Alaska. For the rest of the summer, she participated in Operation “Charger SurfPac 1-73,” during which successive complements of reservists received training in Seventh Fleet operations and the opportunity to train with elements of friendly foreign navies. The capability of the Naval Reserve to augment the fleet on short notice was demonstrated by the airlift which brought in new groups of reservists at regular intervals once the deployment had begun. Southerland reentered San Diego on 30 August 1973, successfully concluding Operation “Charger SurfPac 1-73.” Thereafter, she operated from San Diego along the West Coast. In August 1980, she made last foreign port-of-call to Acapulco, Mexico. A planned transfer to the Ecuadoran Navy fell through due to a fishing rights dispute, and she was placed out of commissio on 26 February 1981.

On 2 August 1997, Southerland was sunk as a test ship for the first live warhead firing of a Penguin anti-ship cruise missile from a helicopter.