Santiago de Cuba, a 1567-ton (burden) wooden side-wheel steamship, was built in 1856 at New York City for commercial use. She was purchased by the U.S. Navy in September 1861, converted to a cruiser and commissioned as USS Santiago de Cuba in November 1861. Sent to the Gulf of Mexico area to enforce the blockade of the Confederate States and protect American shipping, she proved to be a very successful blockader. The first of her many captures was the schooner Victoria, taken in early December. During 1862 and 1863, Santiago de Cuba mainly operated in the western Atlantic, capturing several blockade runners, among them the steamships Columbia (on 3 August 1862), Victory (21 June 1863), Britannia (25 June 1863) and Lizzie (15 July 1863). For several months in 1862, she also served with a special squadron organized to search for the Confederate cruisers Alabama and Florida.

Following an overhaul between December 1863 and June 1864, Santiago de Cuba rejoined the blockade. She captured the steamer Advance on 10 September 1864 and the steamer Lucy in early November. During December 1864 and January 1865 she participated in the two attacks that ultimately captured Fort Fisher, North Carolina, thus bringing to an end most Atlantic Coast blockade running. USS Santiago de Cuba was decommissioned in June 1865 and sold at auction in September. She soon reentered commercial employment and operated as a steamship for the next two decades. She was converted to a barge in 1886 and renamed Marion. The old ship finally passed out of service in about 1899.