USS Seneca, a 691-ton Unadilla class screw steam gunboat built at New York City, was commissioned in October 1861. She participated in the capture of Port Royal and Beaufort, South Carolina, during November and in the blocking of the entrances to Savannah, Georgia, in December 1861. During 1862, Seneca operated along the Confederate coastline from the Carolinas to Florida. She shelled Fort McAllister, Georgia, and assisted in the destruction of the privateer Rattlesnake, in January and February 1863. The following summer, the gunboat took part in attacks on Fort Wagner, near Charleston, S.C.

Seneca was under repair from January into October 1864, then joined the North Atlantic Blockading Squadron. From December 1864 into February 1865, she was engaged in operations to capture Fort Fisher, North Carolina, and to secure the Cape Fear River. USS Seneca was decommissioned at Norfolk, Virginia, in June 1865 and was sold there in September 1868.