Promoted to lieutenant general in North America, he began his service in 1776 under General Sir Henry Clinton with the failed siege of Charleston. He and Clinton then sailed for New York City, where they participated in General William Howe's campaign for New York City. Cornwallis was often given a leading role during this campaign; his division was in the lead at the Battle of Long Island, and he chased the retreating George Washington across New Jersey after the city fell.

in 1780 he inflicted a major defeat on the Continental Army at the Battle of Camden. He also commanded British forces in the March 1781 Pyrrhic victory at Guilford Court House. Cornwallis surrendered his army at Yorktown in October 1781 after an extended campaign through the Southern colonies, marked by disagreements between him and his superior, Sir Henry Clinton.

He surrendered after about three weeks' siege to General Washington and the French commander, the Comte de Rochambeau, on 19 October 1781. Cornwallis, apparently not wanting to face Washington, claimed to be ill on the day of the surrender, and sent Brigadier General Charles O'Hara in his place to surrender his sword formally. Washington had his second-in-command, Major General Benjamin Lincoln, accept Cornwallis's sword.