John Pitcairn made his career in Britain's marine forces, receiving a lieutenant's commission in 1746 and serving during the Seven Years' War. Promoted to major in 1771, he later commanded marines in the Boston garrison as resistance to British authority intensified. His duties joined the marines' normal naval role with the demands of occupying and policing a hostile colonial town.

On April 19, 1775, Pitcairn commanded the advance guard of Lieutenant Colonel Francis Smith's expedition toward Concord. At Lexington, his men confronted Captain John Parker's militia on the common. Witnesses disagreed about the first shot and the orders given; the encounter nevertheless ended with colonial militiamen dead and the British column continuing its mission. During the return march, sustained colonial attacks forced the expedition into a difficult retreat to Boston. Pitcairn's horse was wounded and his pistols were lost, later becoming associated with American officers.

At Bunker Hill on June 17, Pitcairn led marines in the final assault on the American position on Breed's Hill. The troops helped carry the redoubt after earlier British attacks had failed, but he received mortal wounds. His son Thomas, also a marine officer, helped carry him from the battlefield. He died that day and was buried at Boston's Old North Church. Later accounts identified different men as the person who shot him, including Peter Salem, but the identity cannot be established with certainty.