This Regiment was organized at Camp Washburn, Milwaukee, in February and March 1865. Eight of the Companies left the state 22 March and reported at Benton Barracks, St. Louis, Missouri where they were ordered to Paola, Kansas. After they had arrived they were then ordered to other locations where they were needed. Company C was ordered to Lawrence, Company H to Olathe, F and G were retained at Paola, and Companies A, B, D and E were all sent to Fort Scott.

On 8 March Companies I and K departed Wisconsin and arrived at Fort Scott 28 April. Colonel Pearsall was placed in command at Fort Scott early in May, and Major Butt was placed in command of all the troops in Miami and Johnson Counties, with headquarters at Paola. The Regiment was engaged by detachments in procuring timber for fortifications, protecting the country from guerrillas, constructing bridges, erecting new buildings, and many other duties.

On 19 July Colonel Pearsall was assigned to the command of all the troops in and west of Neosho Valley, Kansas with headquarters at Humboldt. Lieutenant Colonel Shears succeeded Pearsall to the command of Fort Scott.

Captain C. W. Felker succeeded to the command of the Regiment and on 10 August the 48th was ordered to Lawrence. It left that place 6 September for Fort Zarah, Kansas where Companies E and G were stationed, and the remainder of the Regiment  moved to Fort Larned, Kansas.

On 1 October the Regiment was divided into detachments and sent to various posts for the purpose of guarding mail and government trains against the Indians.

Companies A, H, E and G were mustered out at Leavenworth 30 December 1865, Companies B, D, F and I on 19 February 1866, and Companies C and K on 24 March.

The original strength of the Regiment was 828. Gained by recruits, 4; total, 832. Loss by death, 9; desertion, 67; discharge, 36; mustered out, 720.