They served primarily in the western theatre of the war, participating in battles and campaigns including the Siege of Vicksburg, the Jackson expedition, the Atlanta campaign, and Sherman's March to the Sea.

It departed Madison for Fort Leavenworth, Kansas, on January 11, 1862, arriving there on February 16.

At Vicksburg the 12th was part of the Third Brigade of the Fourth Division of the Sixteenth Army Corps.

[2] It joined General Sherman's army in the Meridian Campaign, and then returned to Vicksburg until April, when the regiment left for Cairo, Illinois.

[2] On November 15, "Sherman's March to the Sea" commenced, ending on December 10, at Savannah, Georgia.

[5] Some sources say the 12th Wisconsin lost 3 officers and 93 enlisted men killed in action or who later died of their wounds, plus another 3 officers and 224 enlisted men who died of disease, for a total of 323 fatalities, while others say they lost 329.