Lieutenant John Shaw took Enterprise to sea on 17 December 1799, heading for the Caribbean during the Quasi-War with France. American merchant ships were being seized by French privateers, and Enterprise's job was to stop them. She did. In her first cruise she recaptured two American vessels taken by privateers, then returned home with dispatches. Her second Caribbean deployment was more violent and far more productive. On 5 May 1800, she captured the French schooner Citoyen, which lost four killed and eleven wounded. Over the following months she took Le Cigne off Guadeloupe (eleven killed, thirteen wounded), L'Aigle, and Le Flambeau. By the time she captured her last prize of the tour, the schooner La Amour de la Patrie, in late December, Enterprise had established herself as one of the most effective warships in the young American fleet. Shaw, ill and exhausted, turned command over to his first officer, Lieutenant Andrew Sterrett, that October.

Sterrett sailed Enterprise to the Mediterranean for the First Barbary War, reaching Gibraltar in late June 1801. Her encounter with the corsair Tripoli on 1 August became one of the most celebrated single-ship actions in early American naval history. The battle lasted three hours, and three times the Tripolitan crew struck their colors only to open fire again when Enterprise's crew came on deck to cheer. After the third betrayal, Sterrett ordered his men to sink the enemy ship. The Tripolitans begged for mercy, and Sterrett -- listening, as one contemporary account put it, "to the voice of humanity" -- relented. He stripped the vessel of her masts and guns, rigged a single spar with a tattered sail, and sent the wreck home. Enterprise had taken no casualties at all. The lopsided victory stunned Tripoli's naval establishment so thoroughly that sailors deserted every warship the Bey tried to outfit, and the port's corsair fleet sat idle.

Enterprise spent 1802 and 1803 on convoy and patrol duty in the Mediterranean, punctuated by tragedy -- a supply barge capsized at Leghorn in October 1802, drowning a midshipman and three crewmen. When the war with Tripoli resumed, she returned to combat. In November 1803, Lieutenant Stephen Decatur took command. On 23 December, Enterprise and the frigate Constitution captured the Tripolitan ketch Mastico, which was refitted, renamed Intrepid, and used by Decatur in one of the boldest raids of the age: the mission to burn the captured American frigate Philadelphia in Tripoli harbor. Volunteers from Enterprise's crew helped carry it out, destroying the frigate and denying the Tripolitans their most powerful warship. Enterprise then participated in weeks of coordinated bombardments of Tripoli in the summer of 1804 before sailing to Venice for extensive rebuilding, emerging as a substantially different ship -- her schooner rig eventually giving way to that of a brig.

By the War of 1812, Enterprise had been rebuilt and rerigged as a brig at the Washington Navy Yard. On 5 September 1813, she sighted HMS Boxer off the coast of Maine. What followed was a fierce, closely fought action in which both commanding officers were killed. Lieutenant William Burrows of Enterprise and Captain Samuel Blyth of Boxer -- each respected in his own navy -- died leading their crews in an engagement where neither side gave ground easily. Enterprise prevailed and took Boxer as a prize, sailing the captured brig into Portland, Maine, under the guidance of her new captain, Samuel Drinkwater. The people of Portland gave the two fallen commanders a joint funeral with full military honors. Burrows and Blyth were buried side by side in the Eastern Cemetery, near the grave of Commodore Edward Preble. It was a gesture of respect that transcended the war being fought around it.

Enterprise's later years took her back to the Caribbean, where she hunted pirates, smugglers, and slave traders as part of what became the West Indies Squadron. Under Lieutenant Lawrence Kearny in 1818, she evicted the pirate Jean Lafitte from Galveston, Texas. An attack on Cape Antonio, Cuba, in October 1821 broke up a pirate flotilla reportedly commanded by the notorious James D. Jeffers, known as "Charles Gibbs," and rescued three captured vessels. In all, Enterprise took thirteen prizes during her anti-piracy service. Her career ended on 9 July 1823 when she stranded on a reef near Little Curacao Island in the West Indies and broke apart. True to her nickname, every member of her crew evacuated safely. Over twenty-four years, Enterprise had fought in the Quasi-War, the Barbary Wars, and the War of 1812, capturing dozens of enemy vessels and losing remarkably few of her own people. The yacht that defended the 1930 America's Cup was named after her and carried a model of the schooner in its captain's cabin -- a tribute to a ship whose luck never quite ran out, even at the end.