The first Potomac, a frigate laid down by the Washington Navy Yard in August 1819, was launched March 1822. Fitting out was not completed until 1831, when Captain John Downes assumed conunand as first commanding officer. On her first overseas cruise, Potomac departed New York 19 August 1831 for the Pacific station via ihe Cape of Good Hope. On 6 February 1832, Potomac shelled the town of Quallah Batoo, Sumatra in punishment for the capture of mer-chantman Friendship of Salem, Mass. and the massacre of her crew in February 1831. Of the 282 sailors and Marines who landed, two were killed while 150 natives, including the village chieftain, Po Mahomet died for their piracy. After circum-navigating the world, Potomac returned to Boston 23 May 1834.

The frigate next made two cruises to the Brazil station, protecting American interests in Latin America from 20 October 1834 to 5 March 1837, and from 12 May 1840 to 31 July 1842. From 8 December 1844 to 4 December 1845, she patrolled in the West Indies, and again from 14 March 1846 to 20 July 1847 in the Caribbean and the Gulf. During this latter period, she landed troops at Port Isabel, Texas, on 8 May 1846 in support of General Tavlor's army at the battle of Palo Alto. She also participated in the siege of Vera Cruz, 9 to 28 March 1847.

Potomac served as flagship for the Home Squadron 1855-1856. At the outbreak of the Civil War, she departed New York 10 September 1861 for the West Gulf Blocliade Squadron off Vera Cruz. She became the stores ship for the squadron and remained at Pensacola Navy Yard as a receiving ship until 1867, when she was sent to Philadelphia. She remained at League Island Navy Yard, Philadelphia until she decommissioned 13 January 1877. She was sold to E. Stannard & Co. 24 May 1877.