Iroquois sailed for Palermo, Sicily, to protect American lives and property as Giuseppe Garibaldi began his campaign to capture the island for Piedmont-Sardinia.

On board were Confederate ministers James M. Mason and John Slidell, captured earlier by Union ships but released; Comdr.

Iroquois was sent later in 1862 to join Flag Officer David Farragut at the mouth of the Mississippi River, in preparation for his attack on New Orleans, Louisiana.

David Dixon Porter's mortar boats then began a devastating bombardment, and by 24 April the ships were ready to attack.

Iroquois moved abreast the forts as part of the 3rd Division under Captain Henry H. Bell and, after a spirited engagement, passed them and pressed on for the capture of New Orleans, the South's largest and wealthiest city, and key to the Mississippi Valley.

After the great victory Iroquois advanced up the river with Farragut, with the aim of eventually joining Flag Officer Andrew Hull Foote, who was driving southward.

After periodic shelling Flag Officer Farragut, supported by the mortar boats, passed the Vicksburg batteries on 28 June after a heavy exchange of gunfire.

She also took part in the giant search for the Confederate raider Shenandoah, finally arriving Singapore in May 1865 after a long voyage around South America and across the Pacific.

During the local conflicts which engulfed the ports during January, Iroquois stood by to protect American interests, and carried the foreign ministers to Hyōgo 1 February when they were expelled from Osaka.

While in the Delaware River on 7 September of that year, Ordinary Seaman Hugh King jumped overboard and rescued a shipmate from drowning, for which he was awarded the Medal of Honor.

She then sailed for another cruise with the Asiatic Fleet, making the long voyage via the Mediterranean, the Suez Canal, and the Indian Ocean.

Her engines broke down after leaving Honolulu and she spent the next eighty-two days being blown around the Pacific before washing up in Port Townsend, Washington.

The ship was transferred to the Marine Hospital Service at Naval Base Hawaii and served until she recommissioned 13 December 1898, Lt. Charles F. Pond in command.