During the mid-1790s, the young Hull commanded several merchant vessels, losing some to French privateers. He was commissioned a lieutenant in the newly-formed United States Navy in March of 1798 and distinguished himself during the next 2 years while serving on board the frigate USS Constitution in the Quasi-War with France and in the Tripolitan War, from 1801–05. . In 1802, he went to the Mediterranean as first lieutenant of the frigate USS Adams. He later commanded the schooner USS Enterprise and the brig USS Argus, receiving promotion to the rank of Master Commandant in 1804 and to captain in 1806. During the next few years, he supervised the construction of gunboats and in 1809 and 1810 was successively given command of the frigates, USS Chesapeake, USS President and the USS Constitution.
Hull's time on the Constitution was eventful. He took the ship on a European cruise in 1811–12, returning home before the War of 1812 broke out between the United States and Great Britain.
Encountering a British squadron in July 1812 off Egg Harbor, New Jersey, Hull escaped after 3 days and nights in one of the most remarkable chases in naval history. Sailing eastward of Boston, the Constitution met the British frigate HMS Guerriere on August 19. After considerable maneuvering, under fire from the British ship, the American man-of-war delivered its first broadside, within pistol shot range.
In fewer than 30 minutes of close and violent action, the Guerrière was demasted and rendered a total wreck. The helpless hulk was burned, and Hull returned to the mainland a hero. He was recognized as one of the American navy's ablest commanders, and his Constitution became known as “Old Ironsides.”
Hull commanded the Portsmouth Navy Yard at Kittery, Maine, for the rest of the War of 1812, then briefly served on the Board of Navy Commissioners in Washington, D.C. before taking over leadership of the Boston Navy Yard. During 1823–27 he commanded the U.S. squadron operating along South America's Pacific coast. Commodore Hull's next assignment, as Commandant of the Washington Navy Yard, ran from 1829-35. Between 1839-41 he commanded the Mediterranean Squadron. Rendered unfit for further service by age and ill health, he spend the next 2 years on leave.
Hull was noted for the victory of his ship the USS Constitution over the British frigate HMS Guerrière in the War of 1812. The victory united the country behind the war effort and destroyed the legend of British naval invincibility.