In 1846, Preble sailed for New York and joined the Pacific Squadron on the West Coast of the United States, where she participated in the Mexican–American War.

In 1848, Captain James Glynn took her first to Hong Kong and then to Nagasaki, Japan, where she picked up some fourteen American and Hawaiian seamen who had become castaways in that "closed country".

[1][2] In November 1850, she returned to the east coast of the United States, where she became a practice ship for midshipmen until 1857, when she was placed in ordinary service.

She was posted at Head of the Passes on the Mississippi River on 12 October 1861 when the blockading squadron there was attacked by a Confederate States Navy force that included the first ironclad warship, CSS Manassas.

Being a sail-powered ship, she did not join the battle but rather made a swift retreat out the Southwest Pass to safety in the Gulf of Mexico.