Osage, after being refloated and repaired, was transferred to the West Gulf Blockading Squadron in early 1865 for the campaign against Mobile, Alabama.

The original plans for the Neosho-class ships, designed by James Eads, resembled the City-class ironclads with a draft of 5 feet 6 inches (1.7 m), but the successful performance of the Monitor during the Battle of Hampton Roads caused the navy to revise its requirement to include a gun turret.

[1] The ships' main armament consisted of two smoothbore 11-inch (279 mm) Dahlgren guns mounted in a single turret[3] that had an arc of fire of 300°.

Neosho and other warships patrolled the Mississippi and its tributaries to prevent Confederate raiders and flying batteries from ambushing Union supply ships.

"[5] From 12 March to 22 May 1864, Neosho and Osage participated in the unsuccessful Red River Campaign under the command of Rear Admiral David Porter.

She successfully defended the navy transports attacked during the Battle of Blair's Landing on 12 April, driving off the Confederate forces with heavy losses.

During that month she grounded on a sandbar near Helena, Arkansas and could not be refloated even when some of her armor was removed due to the rapidly falling water level.

[8] After being towed to Mound City for more permanent repairs,[9] Osage was transferred to the West Gulf Blockading Squadron on 1 February 1865 for the attack on Mobile, Alabama.

She participated in the Battle of Spanish Fort, defending Mobile from the east, but struck a mine in a previously swept channel and sank rapidly on 29 March.