As the ship was being made ready for a second trip to the Mediterranean, the Secretary of the Navy ordered the vessel to Mexico to assist in a show of force off the coast of Vera Cruz. Here she was flagship of the Home Squadron between February and December 1846, serving in the Gulf of Mexico during the Mexican–American War under the command of Cmdre. David Conner and Capt. Thomas Dulay. Capt. French Forrest later took command when Dulay fell ill. Other notable officers in this cruise were future Civil War rivals Raphael Semmes and John Winslow. The ship oversaw the blockade of the eastern Mexican coast for most of the war. She participated in several aborted attacks on Mexican ports, before running aground on 28 July off the coast of Alvarado. The ship was freed and her ship's company later participated in a raid on Tabasco. The grounding damaged her enough to force her to retire to Norfolk for repairs. Her crew, however, stayed behind and swapped ships with the crew of the sister frigate "Raritan", which had been at sea for three years. The old crew participated in the Siege of Veracruz as part of the Naval battery.