By a joint resolution of Congress on 3 March 1847 Macedonian and sloop-of-war Jamestown were placed in civilian hands to carry food to Ireland during the Great Famine of the late 1840s.

Assigned as part of the East India Squadron under command of Captain Joel Abbot, was one of the ten American ships entering Edo Bay, Japan, on 13 February 1854 during Perry's second visit to negotiate the opening of Japan to foreign trade, remaining as part of the show of force under the Convention of Kanagawa signed at Yokohama on 31 March 1854.

[citation needed] On 26 October 1858 she assisted with the refloating of HMS Curacoa, which had run aground on the Pelican Shoal, off Smyrna, Ottoman Empire.

[2] With the American Civil War looming just ahead, the frigate departed Portsmouth, New Hampshire, for Pensacola, Florida, on 12 January 1861 to join Brooklyn in preventing a possible Confederate attack on the harbor.

From the end of that year through 1870, Macedonian served as school and practice ship for midshipmen at the United States Naval Academy, first at Newport, Rhode Island, then after the civil war at Annapolis, Maryland.