The name "Prince William" was confirmed on 3 April 1780 and she was fitted and coppered at Portsmouth between April and August 1780. She was commissioned under her first commander, Captain Stair Douglas, in April that year, and joined the Channel Fleet under Sir George Darby. She sailed for the West Indies in November 1780 with the fleet under Sir Samuel Hood, and saw action with the fleet at the capture of Sint Eustatius in February 1781, and at the Battle of Fort Royal on 29/30 April 1781. "Prince William" then left the West Indies at the end of the year, sailing to North America and arriving there in October. She was soon back in the West Indies with Hood, and command passed from Douglas to Captain George Wilkinson. She fought with Hood's fleet at the Battle of Saint Kitts on 25/26 January 1782, where she had three men wounded.