USS Bainbridge, a 259-ton brig built at the Boston Navy Yard, was commissioned in December 1842. She operated with the Home Squadron until mid-1844 and then alternated in service with the Brazil and African Squadrons until 1860. In 1859-60 Bainbridge participated in the punitive expedition against Paraguay.

In May 1861, soon after the Civil War began, Bainbridge was sent to the Gulf of Mexico to enforce the blockade of the Confederacy and to protect United States shipping. While in that area in May and June 1862, she participated in the capture of three blockade runners. Following a brief trip north, Bainbridge returned to the Gulf area in August 1862. She encountered a damaging storm at Aspinwall, Columbia (later Panama) in late November 1862 that forced her to jettison much of her equipment, armament and supplies. Repaired at New York in May-August 1863, USS Bainbridge was en route south on 21 August 1863 when she capsized off Cape Hatteras. Only one of her crewmen survived this disaster.

USS Bainbridge was named in honor of Commodore William Bainbridge (1774-1833), one of the leading figures of the early 19th Century U.S. Navy.