When war broke out with Mexico in 1846, the 2nd Infantry Regiment was sent to Camargo, Mexico and joined General David E. Twiggs' Brigade. From September 1846 to December 1847 the regiment campaigned from the Rio Grande to Mexico City, fighting in battles at Veracruz, Cerro Gordo, Contreras, Churubusco, Moline del Rey and Chapultepec.