"Royal George" joined the Western Squadron (also known as the Channel Fleet) under Admiral Sir Edward Hawke in May 1756, just as the Seven Years' War began. Captain Dorrill was succeeded by Captain John Campbell in July 1756, who was in turn succeeded by Captain Matthew Buckle in early 1757. "Royal George" was used as the flagship of Vice-Admiral Edward Boscawen in this period, including flying his flag during the Raid on Rochefort in September 1757. Captain Piercy Brett took command in 1758, and "Royal George" became the flagship of Admiral Lord George Anson in the same year. Brett was succeeded by Captain Alexander Hood in November 1758. The former captain, Richard Dorrill, returned to command the ship the following year, until being invalided in June 1759. Dorrill's replacement was another former captain, John Campbell, who commanded her during the blockade of the French fleet at Brest. She became Sir Edward Hawke's flagship in early November 1759, when his previous flagship, , went into dock for repairs. Hawke commanded the fleet from "Royal George" at the Battle of Quiberon Bay on 20 November 1759, where she sank the French ship "Superbe".