Arriving there on 20 June, the sloop of war joined the Pacific Squadron under Commodore Jacob Jones; and, until 8 September 1831, she cruised the coasts of the Americas to protect the trade and interests of the United States.

Recommissioned on 19 September 1832, St. Louis departed New York on 12 October to base at Pensacola, Florida, as a unit of the West Indies Squadron.

Departing from Norfolk on 11 August 1848, she sailed to Rio de Janeiro, where she served on the South America Station until returning in July 1851.

In January 1861, while serving with the Home Squadron off Vera Cruz, Mexico, St. Louis was ordered to return to Pensacola to stand guard during the turmoil which preceded the outbreak of the American Civil War.

For the next two years, she criss-crossed the Atlantic, cruised the African coast, and patrolled the areas in and around the Canary Islands and the Azores in search of Confederate commerce raiders.

Three days later, sailors and marines from St. Louis went ashore at Boyd's Landing to participate in the combined Army-Navy thrust up the Broad River.

St. Louis then briefly returned to blockade duty before finally sailing to the Philadelphia Navy Yard where she was decommissioned on 12 May 1865.

After being laid up in 1866 and declared unserviceable, she became a receiving ship at League Island and continued this duty until 1894 when she was loaned as a training vessel to the Naval Militia of the State of Pennsylvania.

She was finally struck from the Navy list on 9 August 1906 and sold for scrapping, on 5 June 1907, to Joseph G. Hitner of Philadelphia.