Pawnee spent the first three months of 1861 in Washington, D.C., and was sent on an expedition to Charleston, South Carolina 6 April to relieve Major Robert Anderson's garrison at Fort Sumter.

[2] Arriving at Norfolk the night of 20 April, she found that all ships, save USS Cumberland, had been scuttled, so an attempt was made to destroy the Naval stores and the dry dock.

[3] From May to August 1861 Pawnee, based at Washington, operated on the Potomac River, furnishing protection for surveying parties, bombarding Confederate shore batteries, convoying vessels and performing general blockade duty.

On 29 October Pawnee sailed from Hampton Roads on a joint military-naval expedition to Port Royal Sound on the South Carolina coast, which resulted in the capture of an invaluable base for the Union blockade and future amphibious operations.

Pawnee departed Philadelphia 6 January 1863, took ironclad USS Patapsco in tow at Hampton Roads, and arrived off Port Royal, South Carolina 10 February.

For the remainder of the war, she operated with the South Atlantic Squadron in coastal reconnaissance off the southern states, engaging shore installations, and watching for blockade runners.

Between 1 February and 18 June 1864, she assisted in the capture of Confederate steamers General Sumter and Hattie Brock along with their valuable cargoes of cotton, turpentine, rosin and railroad iron.

Sailing from Portsmouth 24 April, she joined her squadron off Rio de Janeiro and operated in that area for two years protecting American citizens and their property during the war between Brazil and Paraguay.