USS Louisville, a 512-ton Cairo class ironclad river gunboat, was built at Saint Louis, Missouri, and commissioned in January 1862. During February - June 1862, while serving in the U.S. Army's Western Gunboat Flotilla in a successful campaign to secure the upper Mississippi and its tributaries, she participated in actions at Fort Donelson, Island Number Ten, Memphis and Vicksburg.

Transferred to the Navy in October 1862, Louisville took part in operations above Vicksburg during the rest of that year and into 1863. In April 1863, she was one of the Federal ships that ran past Vicksburg's batteries and later engaged Confederate fortifications at Grand Gulf. In March, April and May 1864, Louisville was a unit of the squadron operating in support of the Red River campaign. She remained active on the Western Rivers until the end of the Civil War. Decommissioned in July 1865, USS Louisville was sold in November 1865.