Mohawk sailed at once for South America to take part in Flag Officer William B. Shubrick's 18-ship Paraguay expedition, attempting to gain apology for the 1855 firing upon survey steamer Water Witch.

Arriving Asunción with the squadron 25 January 1859, Caledonia took position above Rosario in Río de la Plata, ready for operations while negotiations were conducted.

Mohawk operated against pirates and slavers off the east coast and in the Caribbean through 1861, capturing slave ship Wildfire in Old Bahama Channel 28 April 1860, and delivering the prize to Key West where the crew was imprisoned.

[1][2] From 15 November on Lieutenant Craven in Mohawk, with the steamer Wyandotte, defended Forts Jefferson and Taylor at Key West, from actions of "bands of lawless men", a farsighted action that enabled the Union to retain that vital Florida base, so valuable during the forthcoming naval operations in the American Civil War.

Ordered north for repairs 27 June 1864, on 6 July she reported to Commodore Cornelius Stribling at Philadelphia Navy Yard.