After shakedown training out of Guantánamo Bay, Cuba, and the usual post-shakedown availability, Wilkinson departed her home port, Newport, Rhode Island, on 21 February 1955—with Rear Admiral Arleigh Burke, Commander, Destroyer Force, Atlantic Fleet (and soon to become the Chief of Naval Operations) and members of his staff embarked—and carried Admiral Burke on an inspection tour that included visits to San Juan, Puerto Rico; St. Thomas, Virgin Islands; Guantánamo Bay and Havana, Cuba; and Key West, Fla.

After successfully completing her sea trials for her newly installed 3 inch / 70 caliber battery, Wilkinson conducted underway training out of Guantánamo Bay.

The ship's performance during the fiscal year 1956 earned her the Battle Efficiency "E." In July 1956, Wilkinson departed Newport, bound for San Diego, Calif., and duty with the Pacific Fleet.

En route to her new home port, the frigate visited Havana; Balboa, Canal Zone; and Buena Ventura, Colombia; before she became flagship of Commander, Destroyer Squadron (DesRon) 17—the first ship of her type assigned to the Pacific Fleet.

One highlight of that period occurred on 14 September 1956, when Wilkinson headed a veritable "armada" of 70 fighting ships during a 1st Fleet review off Long Beach, in what some called the largest naval parade on the west coast in 22 years.

Later, during part of May, Rear Admiral Chester Wood, Commander, Cruiser-Destroyer Force, Pacific Fleet, embarked in Wilkinson for air defense and ASW exercises.

Wilkinson's home port was changed from San Diego to Long Beach in July 1957, and the destroyer leader entered the naval shipyard there in February 1958 for extensive modifications to her power plant.

She operated locally during October and November and, after a month-long leave and upkeep period in December, was deployed to WestPac for the third time, departing Long Beach on 3 January 1961.

Calling at the Mexican ports of Acapulco and Salina Cruz en route, Wilkinson transited the Panama Canal on 29 June and arrived at Newport on 5 July.

After a pre-overhaul tender availability, Wilkinson visited New York City for four days; off-loaded ammunition subsequently at Earle, N.J.; and proceeded to Boston for an overhaul which lasted until 5 February 1966.

At 08:09, Wilkinson began closing the Nationalist Chinese merchantman Chungking Victory to receive the surviving crew members of Viking Princess—a process completed by 09:14.

Underway on 15 January 1967, Wilkinson headed south to Argentine waters, subsequently taking part in the Argentinian naval review at Mar del Plata from 4 to 8 February on the occasion of the celebrations commemorating the sesquicentennial of Argentina's independence.

Returning to Newport on 5 March, Wilkinson then proceeded to the Bethlehem Steel Shipyard at East Boston, Mass., where she received a data acquisition system for her sonar equipment.

The ship put into Port Everglades to take on fuel on 3 October and was standing back out on the 5th when a weak cleat snapped while the motor whaleboat was being secured for sea.

After a pre-overhaul period of availability alongside Yosemite (AD-19), Wilkinson entered the Boston Naval Shipyard on 13 September for her regular overhaul that rounded out the year and lasted into June 1969.

Following her sea trials, Wilkinson got underway for Narragansett Bay for sonar tests, before she set course for Earle, N.J., to load ammunition in preparation for refresher training.