This Regiment was organized in October 1861. It was mustered into US service and left the state 30 March 1862 for Pittsburg Landing, Tennessee and reached there 5 April.

The next morning, with absolutely no instruction in the manual of arms and but little drill, it was ordered to stop the enemy's advance at Shiloh. It fought bravely, losing 24 killed, 82 wounded, and 174 became prisoners. Governor Harvey said, "Many Regiments may well covet the impressions which the 18th Wisconsin left of personal bravery heroic daring and determined endurance. "

In Mississippi it took part in the siege of Corinth, encamping there after the surrender; then Bolivar until 17 September when it was ordered to Iuka to reinforce General Rosecrans, but was immediately returned to the defense of Corinth that was being threatened by the enemy.

On 1 October it met the advance of Confederate Major General Earl Van Dorn and fell back to the protection of Smith's Bridge the following day. On the 3d, when the enemy appeared in force, the Regiment burned the bridge, rejoined its brigade at the railroad, and retained its position until overwhelming numbers compelled it to again fall back.

It joined in pursuit of the enemy after the battle of Corinth, and on 2 November proceeded to Grand Junction, Mississippi. In the movement southward it went first to Holly Springs, Tennessee, then back to Grand Junction, then on to Moscow and Memphis, Tennessee and from there by boat to Young's Point, Louisiana where it remained until 9 February 1863.

In the advance to Vicksburg it took position in the battle of Champion's Hill, and reached Vicksburg on 20 May. It deployed men as sharpshooters to cover the assault on the 22nd and on 4 June occupied trenches where it remained until the surrender.

It was assigned to guard duty until 11 September when it was sent to Memphis, then to Corinth finally arriving at Chattanooga 19 November. It joined in the attack on Missionary Ridge, Tennessee and was assigned to guard duty at Bridgeport, Alabama during the greater part of December.

It went to Huntsville, Alabama on 25 December, remained there until 1 May 1864, then went to Whitesburg, Kentucky for guard duty until 19 June, and was in camp, garrison and guard duty in Georgia and Tennessee until September. In October it aided in the defense of Allatoona against repeated assaults of a superior Confederate force. 

A furlough was granted reenlisted veterans on 12 November, and the recruits and non-veterans were temporarily assigned to the 93rd Illinois, which accompanied Sherman's Army to Savannah. The veterans were ordered to Nashville, reaching there 11 January 1865, and were then sent to New Berne, North Carolina where they encamped until the last of March, when they joined Sherman at Goldsboro, North Carolina and took part in the march to Richmond, Virginia.

The Regiment participated in the grand review at Washington, DC and was mustered out at Louisville, Kentucky 18 July 1865.