"Louisville" assisted the Army in the capture of Fort Donelson on the Cumberland River 14 to 16 February 1862. From 1 to 5 March, she aided in the occupation of Columbus, Kentucky, the "Gibraltar of the West." Departing Cairo, Illinois, 14 March, she served in the capture of Island No. 10 and New Madrid, Missouri, through 7 April, and helped to prevent southern ships from ascending the river.