While on such a mission about 110 miles (180 km) west of Gibraltar, Chauncey was involved in a fatal collision with a British merchantman, SS Rose, on the night of 18–19 November.

Following shakedown training along the west coast and post-shakedown availability back at the Bethlehem Steel Co., Wedderburn departed San Francisco on 21 June in company with Fieberling (DE-640).

The two warships arrived in Pearl Harbor six days later, and Wedderburn joined Task Unit (TU) 19.3.2 with which she served briefly on plane guard and anti-submarine duty.

On 1 July, the destroyer continued her voyage west to Eniwetok in the Marshall Islands where she joined Task Force (TF) 53 for the second assault of the Marianas operation, the battle of Guam.

She arrived off Guam on 22 July, the day after the initial assault on that island and, for the next three weeks, performed yeoman service protecting the invasion fleet—upon which the battle ashore depended—from the threat of Japanese submarine attack.

There, she was reassigned to the antisubmarine screen of a fast carrier task group, TG 38.2, built around Intrepid (CV-11), Hancock (CV-19), Bunker Hill (CV-17), Cabot (CVL-28), and Independence (CVL-22).

Wedderburn continued to guard the fast carriers while they operated off the northeastern shore of Luzon providing distant air support for the Leyte invasion.

That same day, planes from Wedderburn-protected carriers opened the battle striking at the enemy's Center Force, commanded by Vice Admiral Takeo Kurita—while it traversed the Sibuyan Sea toward the San Bernardino Strait.

Instead, she participated in the final phase of the battle, against Ozawa's force, though her role remained one of support for the carriers which she screened against submarine attack while she rescued their downed aviators.

Wedderburn, however, suffered only minor damage and participated in the search for survivors of Hull (DD-350), Monaghan (DD-354), and Spence (DD-512) though she did not engage in any actual rescue operations.

Early on 10 February, the fast carriers again stood out of Ulithi to provide air support for the assault on Iwo Jima in the Volcano Islands.

During the current two-day attack, the American planes made 138 sorties in which their pilots claimed to have sunk three picket boats and an escort carrier as well as to have destroyed over 700 enemy aircraft.

Following the raid, Wedderburn escorted the carriers south to Iwo Jima where she participated in shore bombardments and patrolled against submarines in TF 51's transport area.

On 23 February, she departed Iwo Jima and rejoined TG 58.2 as it headed off north with the rest of TF 58 for another round of strikes on the Japanese home islands.

The fast carriers continued to steam on station off Okinawa protected by Wedderburn and her colleagues but, on 7 April, launched a series of search and attack sorties which ultimately sent the mighty Japanese battleship to the bottom along with light cruiser Yahagi and four of the escorting destroyers.

After that scrape, TF 58 concentrated its efforts on supporting the troops ashore and defending itself and the invasion force from the final onslaught of Japanese air power.

On 18 May, the destroyer departed Ulithi to escort Missouri (BB-63) to Guam to pick up Admiral William F. Halsey who was scheduled to take command of the naval forces off Okinawa later that month.

For the remainder of World War II, she screened various task groups of TF 38 first while they continued support for the Okinawa operation and, later that summer, when they went on their final rampage in the Japanese home islands.

Immediately following the war, the destroyer served with the occupation forces around Tokyo Bay, escorting Japanese merchant ships, supervising mine-clearing operations, and making hydrographic surveys.

For the most part, though, her duties consisted of blockading the coastline of Korea and providing gunfire support for the United Nations troops operating ashore.

Once again, she divided her time between blockading and gunfire support missions along the Korean coast and escort duty with the fast carriers as well as short periods with the Taiwan Strait patrol.

During the 1958 deployment, she visited Sydney, Australia, in addition to her usual ports of call farther north and participated in the multinational SEATO exercise, Operation Ocean Link.

The remainder of her deployments were more routine in nature consisting of plane guard duty with TF 77, port visits, training exercises, and periods of time with the Taiwan Strait patrol.

After a month of post-deployment stand-down followed by four weeks of local operations out of San Diego, she entered the Long Beach Naval Shipyard for a month-long availability.

In June and July, she embarked NROTC midshipmen for their summer cruise, during which she visited San Francisco and the islands of Kauai and Oahu in Hawaii.

Returning to San Diego on 4 August, the warship conducted three weeks of repairs and then resumed training operations which continued until she began preparations for another Far Eastern cruise in November.

She continued in that role until 2 April when she was detached and reassigned to Task Unit (TU) 70.8.9 to conduct gunfire support missions near Danang and Quang Tri.

After a week's liberty call at Hong Kong and repairs at Yokosuka, Wedderburn headed home on 3 June and arrived in San Diego 10 days later.

During the first two months of 1967, Wedderburn conducted extensive refresher training exercises and, during March and early April, made preparations for overseas movement.

Her guns helped the marines ashore complete Operation Bear Chain, an amphibious assault by Special Landing Force "Bravo" near Quang Tri City.