In October 1780, O'Hara was promoted to brigadier and became commander of Brigade of Guards. He became Lieutenant General Charles Cornwallis' second-in-command and good friend. During Cornwallis' pursuit of Major General Nathanael Greene to the Dan River, O'Hara distinguished himself at Cowan's Ford, North Carolina on 1 February 1781. He also led the British counterattack at the Battle of Guilford Courthouse on 15 March 1781, which led to General Greene withdrawing from the field of battle. He was severely wounded during this battle, but was able to remain with the army as it moved toward Yorktown, Virginia. His nephew, who was a lieutenant of the artillery, was killed during the battle.

General O'Hara represented the British at the surrender of Yorktown on 19 October 1781, as Cornwallis' adjutant, when the latter pleaded illness. He first attempted to surrender to French Comte de Rochambeau, who declined his sword and deferred to General George Washington. Washington declined and deferred to Major General Benjamin Lincoln, who was serving as Washington's second-in-command and had surrendered to General Clinton at Charleston in May 1780. O'Hara was exchanged on 9 February 1782, and was sent to the Caribbean in command of a detachment of reinforcements. Following the conclusion of the war with the Treaty of Paris he returned to Britain having been promoted to major general.