The 3rd Minnesota was mustered in by companies at Fort Snelling, Minnesota, between October 2 and November 14, 1861, and was sent to Kentucky on November 14, 1861. It remained on garrison duty in Kentucky and Tennessee until most of the men were captured by Nathan Bedford Forrest at Murfreesboro, Tennessee, on July 13, 1862. They were subsequently paroled and sent to Benton Barracks at St. Louis, Missouri, to await parole.
The regiment was formally exchanged on August 27, 1862, and moved home to Minnesota, where it participated in the suppression of the Dakota War of 1862. In September 1862, it participated in Col. Henry Hastings Sibley's campaign against the Sioux, culminating in the defeat of the Indians at the Battle of Wood Lake on September 23. At the end of the brief campaign, the regiment returned to Fort Snelling to reorganize.
The 3rd Minnesota returned to garrison duty in Kentucky and Tennessee in January 1863 and remained there until joining in the Siege of Vicksburg until the surrender of the defenders on July 4, 1863. The regiment then participated in the campaign to capture Little Rock, Arkansas, from August 13 to September 10, 1863, and remained in garrison there after the fall of the city until April 28, 1864.
Enough of the soldiers of the regiment reenlisted in January 1864 to Veteranize it. Part of the 3rd Minnesota participated in an expedition up the White River to Augusta from March 30 to April 3, 1864, culminating in the Battle of Fitzhugh's Woods on April 1, 1864. The regiment remained in various garrisons to the end of the war.
The 3rd Minnesota Infantry suffered 17 enlisted men killed in action or who later died of their wounds, plus another 4 officers and 275 enlisted men who died of disease, for a total of 296 fatalities.