The 4th Minnesota Infantry participated in Maj. Gen. Henry Wager Halleck's advance on and Siege of Corinth, Mississippi, from May 18 to May 30, 1862.

The regiment participated in Ulysses S. Grant's Central Mississippi Campaign from November 1862 to January 1863.

The regiment performed garrison duty at Vicksburg followed the surrender, remaining at that location until September 12, 1863.

The regiment participated in the Third Battle of Chattanooga from November 23–27 1863, then was on garrison duty at Bridgeport and Huntsville in Alabama, until June 1864, having Veteranized during the spring of 1864.

The 4th Minnesota Infantry suffered 3. officers and 58 enlisted men killed in action or who later died of their wounds, plus another 3 officers and 175 enlisted men who died of disease, for a total of 239 fatalities.