Although St. Lawrence was laid down in 1826 by the Norfolk Navy Yard in Portsmouth, Virginia, she remained uncompleted on the ways until work on her, interrupted by a shortage of funds, was resumed during the Mexican–American War (1846–1848).

On 29 August, the Navy Department, at the request of the Prussian Minister to the United States, directed Paulding to "take on board a Mister H. W. Foster and rate him Master's Mate."

Before departing Bremerhaven, St. Lawrence received on board four Prussian midshipmen for training, and they served on the frigate, learning the customs, discipline, and seamanship of the United States Navy.

In July, she returned to Bremerhaven where Paulding discharged the German midshipmen on the 10th, since Prussia was then at war with Denmark, the next country on the frigate's itinerary.

In the summer of 1850, when tension in Europe began to subside, St. Lawrence was ordered to proceed once more to the Baltic for a short cruise before returning home.

On her return voyage from this interesting assignment, she gave the United States chargé d'affaires in Portugal passage from Southampton to Lisbon.

Recommissioned on 22 September 1856, St. Lawrence sailed for the Atlantic coast of South America to become flagship of the Brazil Squadron early the next year.

She sailed for the Confederate coast eight days later but was delayed in the lower Delaware River by low tides until 8 July when she finally put to sea.

Survivors from the schooner, which sank half an hour later, revealed that their ship had been the Confederate privateer, Petrel, of Charleston, South Carolina.

After replenishing her ammunition, provisions and water at New York, the frigate sailed for the Virginia Capes for service in the North Atlantic Blockading Squadron.

She reached Hampton Roads on 6 March and was on hand when Confederate ironclad, Virginia, (formerly USS Merrimack) attacked Union warships there two days later.

On that fateful afternoon, gunboat USS Cambridge, came alongside, with word of the ram raid, and towed St. Lawrence toward the scene of the action.

As the two ships passed Sewell's Point, Southern batteries there opened fire with shot and shell and made several hits, but did no serious damage.

While Cambridge and tug, USS Young America, were attempting to refloat the frigate, Virginia opened fire from some 900 yards distance.

One 80 pound (36 kg) shell from Virginia penetrated St. Lawrence's starboard quarter just above the water line and did considerable damage to her wardroom pantry and to the Assistant Surgeon's stateroom.

In Robert Conroy's alternate history novel 1862, St. Lawrence is sunk by the Royal Navy steam sloop-of-war HMS Gorgon as revenge for the Trent Affair, bringing the United Kingdom into the American Civil War on the side of the Confederacy.