After several years of service in the Home Squadron, during which she performed experiments crucial to development of the steam Navy, Mississippi joined the West Indian Squadron in 1845 as flagship for Commodore Perry. During the Mexican-American War, she took part in expeditions against Alvarado, Tampico, Pánuco, and Laguna de los Términos, all successful in tightening American control of the Mexican coastline and interrupting coastwise commerce and military supply operations.