Organized in the fall of 1864, the 49th Missouri Volunteer Infantry Regiment served in northern Missouri and participated in the defense of Jefferson City during the Price Raid. During the winter of 1864/1865 the companies of the 49th garrisoned towns throughout northern Missouri and constantly patrolled against guerrillas.
Then it was sent south and participated in the campaign against Mobile, Alabama and the siege of Spanish Fort. After the end of the war the regiment was part of the occupation of Montgomery, Alabama till July 14 when Companies A, B, C, D, E, F, G, and I were ordered to St. Louis and mustered out August 2, 1865. Companies H and K remained on duty at Eufaula, Alabama until being mustered out on December 20, 1865.