USS Isaac Smith, a 453-ton (burden) screw steam gunboat, was built at Nyack, New Jersey, in 1851 as a commercial steamer of the same name. She was purchased by the U.S. Navy in September 1861 and placed in commission in October. Isaac Smith's first operation was the capture of Port Royal, South Carolina, in November 1861, during which she engaged Confederate warships and shore batteries. In January 1862 she took part in an expedition in Wassaw Sound, Georgia, and beginning in March was active in the waters of northeastern Florida. Her boats captured a blockade runner there in April.

Isaac Smith went north for repairs in August 1862, but returned to the South Atlantic Blockading Squadron in October. She was then assigned to operate in the Stono River, South Carolina. While making a reconnaissance in that river on 30 January 1863, she was caught by enemy shore batteries and badly battered. With eight of her crew killed and many more wounded, USS Isaac Smith was forced to surrender. Taken into Confederate Navy service under the name Stono, she was wrecked near Fort Moultrie, S.C., while attempting to run the blockade of Charleston on 5 June 1863.