Levant sailed from New York on 1 April 1838 for four years' service in the West Indies Squadron protecting American interests in the Caribbean and South Atlantic.

William N. Smith in command, Levant sailed on 13 November for Rio de Janeiro, the Cape of Good Hope, and Hong Kong, where she arrived to join the East India Squadron on 12 May 1856.

On 15 November, while in the process of withdrawing this force, Commander Foote was fired on while passing in a small boat by the "Barrier Forts" on the Pearl River below Canton.

Levant, close in through most of the action, received the major part of the Chinese bombardment, with 22 shot holes in her hull and rigging, one man dead, and six injured.

In May 1860, Levant was ordered to the Hawaiian Islands at the request of the Secretary of State to investigate the disbursement of relief funds to American merchant seamen.

After receiving a state visit by King Kamehameha IV at Honolulu on 7 May, and investigating at Lahaina, Maui, and Hilo, Hawaii, Levant sailed for Panama on 18 September 1860, but never made port.

Commodore Montgomery reported that a violent hurricane had occurred in September 1860 in a part of the Pacific Ocean which Levant was to cross.

It was corked and contained a card that read in part: "Pacific Ocean" "Levant" "Written by the last remaining" "three" "in a boat" "God forgive us".

On 24 July 1861, the United States Congress passed a law to compensate the widows and orphan children of the officers, seamen, marines and others who were lost with the Levant.

In 1863, when Edward Everett Hale wrote the patriotic short story The Man Without a Country, the announcement of the death of the exiled Philip Nolan while at sea is said to have been while he was aboard the USS Levant on 11 May 1863.