Nashville had run the Union blockade on 21 October and docked at Southampton after crossing the Atlantic, becoming the first vessel to show the Confederate flag in English waters.

She finally weighed anchor and departed on 3 February 1862, but Tuscarora was unable to pursue her as English law required that two belligerent vessels leave port separated by not less than 24 hours.

On June 23, she received orders to sail immediately for England and to deploy off the coast in search of the recently launched Confederate raider CSS Alabama.

Tuscarora reconnoitered the southern coasts of England and Ireland and scoured the Irish Channel without finding any trace of the vessel.

During August, Tuscarora searched for Confederate raiders off the Grand Banks, Newfoundland, but encountered none before she returned to Boston on 3 September.

She was transferred to the blockade off Ossabaw Sound, Georgia, on 5 March 1865, and escorted Jefferson Davis, his family, and other captured Confederate officials aboard the steamer William P. Clyde from Port Royal to Hampton Roads on 16 May to 19 May.

She also touched at Fiji, where she received payment of awards made to United States citizens in 1855 and 1858 for injuries and losses sustained as a result of acts of the natives.

Tuscarora returned to South America in 1868 and was placed at the disposal of the Chilean government to assist victims of the great earthquake which had occurred on 18 November 1867.

In February 1869, she investigated the imprisonment of the United States consul at Buenaventura, Colombia, and moved to Valparaíso at the end of the month.

She cruised off the coast of Cuba in June and escorted the ironclads Wyandotte, Ajax, and Manhattan from New Orleans to Key West.

After her arrival on 25 June, Tuscarora departed San Francisco and surveyed the sea floor off the northwest coast to determine a suitable route for a submarine cable.

Theodore F. Jewell, quelled a large riot that followed the election of King David Kalākaua at the request of U.S. Minister Henry A. Peirce.

Tuscarora was transferred to the North Pacific Station on 11 October 1874 and left for Honolulu on 1 November with orders to take soundings of the ocean bottom every 30 nautical miles (60 km).

She left in September and performed survey work in the South Pacific, visiting the Fiji Islands, Australia, and Samoa.

Tuscarora was recommissioned at Mare Island on 10 January 1878, and was assigned special oceanic survey work off the western coasts of Central and South America.