USS Grayson, a 1620-ton Gleaves class destroyer built at the Charleston Navy Yard, South Carolina, was commissioned in February 1941. For the remaining ten months of an increasingly tense "peace" she took part in Atlantic Ocean Neutrality Patrols, convoy escort duties and other "short of war" activities. After war began with Germany, Italy and Japan, Grayson steamed through the Panama Canal to join the Pacific Fleet and, in April 1942, took part in the Doolittle raid on Japan.

Grayson received an overhaul during the next few months but reentered the combat zone in time to escort the aircraft carrier Enterprise during the invasion of Guadalcanal and Tulagi in early August 1942 and in the Battle of the Eastern Solomons later in that month. She suffered light damage and some casualties from Japanese air attack in the latter action. The destroyer was in the south Pacific well into 1943, supporting the long and bloody campaign to hold Guadalcanal and, on 18 October 1942 rescued survivors of her sunken sister ship, USS Meredith, and recovered the abandoned tug Vireo. Four months later, while escorting a Guadalcanal-bound convoy in the early morning darkness of 17 February 1943, Grayson helped to repel an enemy torpedo plane attack.

Shipyard work kept Grayson out of the combat zone during mid-1943, but she was back in the south Pacific by late September. Early in October she took part in battles with barges evacuating Japanese forces from Kolombangara. In the spring and early summer of 1944 she participated in amphibious assaults in the Admiralty Islands and along the northern shore of New Guinea. The invasion of the Palaus was her assignment in September 1944, and during mid-October she was present when the cruisers Houston and Canberra were towed out of danger after they had been torpedoed off Formosa.

For the rest of 1944 and through the first five months of 1945, Grayson was employed on patrol and rescue duty in the central Pacific. She was overhauled during June-August 1945 and did not rejoin the combat fleet until the fighting had ceased. Almost immediately sent back to the U.S., Grayson arrived at her birthplace, Charleston, S.C., in time to participate in the great Navy Day celebrations in October 1945. Decommissioned in February 1947, she was in the Reserve Fleet for more than two decades. USS Grayson was stricken from the Naval Vessel Register in February 1971 and was sold for scrapping in November 1972.