She was outfitted as a gunboat, with both a 20-pounder rifle for horizontal firing, and two howitzers for shore bombardment, and assigned to the Union blockade of the waterways of the Confederate States of America.

On 6 February, she captured blockade runner, Margaret, off Isle of Breton, Louisiana, as the sloop was attempting to escape to sea laden with cotton.

During the first weeks in April, Sciota, supported Farragut's efforts to get his deep draft ships across the bar off Pass a L'Outre and into the Mississippi River.

She attacked and passed the Confederate forts at Vicksburg, Mississippi on 28 June when Farragut raced by that riverside stronghold to join Flag Officer Charles H. Davis' Western flotilla.

Since the Army was unable to provide the troops necessary for joint operations against Vicksburg, Farragut decided to return down river to turn his attention to the blockade in the western gulf.

On 3 January 1863, Farragut ordered gunboats, Sciota, Cayuga, and Hatteras to Galveston, Texas which had just been captured by the South in a surprise attack shortly after midnight on New Year's Day.

On the last day of 1863, she and Granite City made a reconnaissance from Pass Cavallo, and landed soldiers on the gulf shore of Matagorda Peninsula in action continuing through 1 January 1864.

Reporting on the operation, Lt. Col. Frank S. Hasseltine wrote: Captain Perkins, of the Sciota, excited my admiration by the daring manner in which he exposed his ship through the night in the surf till it broke all about him, that he might, close to us, lend the moral force of his ... guns ... and by his gallantry in bringing us off during the gale.On 21 January 1864, Sciota and Granite City joined several hundred troops in a reconnaissance of the Texas coast.

On 27 October, she captured Prussian schooner, Pancha Larispa, attempting to run through the blockade into either Velasco or San Luis Pass, Texas.