The expedition from Cork, Ireland, with Campbell and his force, arrived off the coast of Cape Fear, North Carolina in April and May 1776. It then moved to attack Charleston, South Carolina from the sea. He was involved at Sullivan's Island, although his unit avoided direct action. He was then redeployed to Staten Island, New York on July 21. Next, he was at the battles at Long Island, Paulus Hook, Fort Montgomery, and the raid on Egg Harbor. Shortly after the 57th's return to New York City, Campbell was promoted to Brigadier General and transferred to a staff command. In October 1778, Campbell received a communication from Lord George Germain to proceed to Pensacola in the Province of West Florida and take command of the British troops there. On February 19, 1779, Campbell was promoted Major General, and on March 22, he was given complete authority over all troops in the Province of West Florida.

Early in March 1781, the long-awaited Spanish attack on Pensacola began. On March 21, Campbell made a humane proposal to Galvez that the town and garrison of Pensacola should be spared. Campbell inspired his troops to defend Fort George. However, without naval protection nor adequate artillery to engage a counter assault, the Spanish artillery fire breached the ramparts on May 8, and struck a powder magazine. A powerful flotilla of warships neutralized outer British defenses and began an amphibious siege of the town on May 9. Campbell surrendered Fort George the next day. Under generous terms, Galvez allowed the British troops, including Campbell, to return to New York. Campbell remained in British-held New York City until the British left under the Treaty of Paris on Evacuation Day, November 25, 1783. In 1783, he replaced General Guy Carleton as Commander-in-Chief, North America, a post he held until 1787.