This Regiment was organized at Racine in June 1861, with a numerical strength of 1,047. It was mustered into United States service 2 July and was initially used in suppressing bank riots in Milwaukee and Watertown, Wisconsin.

It left the state 15 July and on the refusal of the railroad company to transfer it from Corning to Elmira, New York it seized the train and ran it to Elmira. It went into headquarters at the Relay House, Maryland and later joined the Maryland "Eastern Shore Expedition", arriving in Baltimore in December.

On 19 February 1862, it left for Fortress Monroe, Virginia to join the New Orleans Expedition, but was sent instead to Ship Island, Mississippi until 16 April. On 28 April Companies E and G were landed 10 miles from Forts Jackson and St. Philip, Louisiana after rowing 5 miles and drawing 30 boats loaded with arms and ammunition a mile and a half, while wading in mud and water waist deep.

The Regiment, with the 31st Massachusetts, was first landed in New Orleans and took forcible possession of the Custom House. The 4th Wisconsin was then occupied in scouting duty in detachments until July 26, when it was sent to Baton Rouge, Colonel Paine taking command of the troops there with orders to burn the city with the exception of the state library, paintings, statuary and charitable institutions.

This order was afterwards revoked on Colonel Paine's representation to General Butler "that the town would be useful to our army for further military operations." The town was fortified thoroughly by the Regiment, which was later ordered to Carrollton, near New Orleans, Company G being detached for service with the heavy artillery, and 40 men were also transferred to the 2nd U. S. Artillery. The winter and spring were devoted to picket duty and small expeditions through Mississippi.

The Regiment took a prominent part in the battle of Fort Bisland near Brashear City, Louisiana in April 1863. It was then sent to Opelousas, where it met and defeated a large mounted force of the enemy.

By order of General Banks, the Regiment was mounted and thereafter served as Cavalry. It was in numerous skirmishes until ordered to Port Hudson, Louisiana in May as part of the attacking force. It took part in the first assault and reached the ditch surrounding the fortifications, having been temporarily dismounted. It was in the second assault on 14 June, during which the Regiment lost 140 of the 220 men engaged in the charge.

It returned to Baton Rouge 25 July, and spent most of 1864 engaged in picketing, foraging and preserving the peace in that area, occasionally capturing or dispersing small bands of Confederate Cavalry and guerillas. On 27 November 1864, it formed part of a Cavalry force to keep the enemy near Mobile, Alabama from advancing toward General Sherman.

The winter was passed at Baton Rouge and the Regiment was sent to Mobile, Alabama in April 1865. After Mobile surrendered in April the 4th was sent on a 70-day expedition through Georgia, Alabama and Mississippi. In July it was ordered to Texas and remained there until May 1866, to prevent smuggling, guard against the Indians and preserve the peace.

The Regiment was mustered out 28 May 1866. Its original strength was 1,047. Gained by recruits, 982; substitutes, 16; reenlistments, 260; total, 2,305. Loss by death, 350; missing, 23; desertion, 74; transfer, 2; discharge, 474; mustered out, 754.