Mustered into the United States service on December 24, 1861, at Camp Sigel, Jefferson county, Kentucky. It was assigned immediately to the Department of the Cumberland, and its active service commenced. It was placed in Hazen's Brigade of Nelson's Division, in which command it fought at Shiloh, losing 10 killed, and 93 wounded, out of about 450 in action. In that battle the regiment, under command of Colonel Whitaker, made a gallant fight; it captured there three pieces of artillery, the Colonel cutting down one of the cannoniers with a bowie-knife, just taken from a captured man. After sharing in the siege operations about Corinth, the regiment participated in the long, wearisome marches of Buell's Army in the summer and fall of 1862, and after marching through Northern Alabama, Tennessee, and Kentucky, was engaged at the battle of Stone's River. It was then in Palmer's Division, its loss in that battle amounting to 13 killed, 90 wounded, and 10 missing, Lieutenant-Colonel George T. Cotton being among the killed. The regiment encountered its hardest fighting and severest loss at Chickamauga, where, out of a small number present, it lost 12 killed, 95 wounded, and 11 missing. During the Atlanta campaign the Sixth was in Hazen's (2d) Brigade, T. J. Wood's (3d) Division, Fourth Corps, and was prominently engaged in all the battles of that command. It was mustered out on November 2, 1864, its term of service having expired. The recruits and reënlisted men with unexpired terms, remaining in the field, were transferred to the Fourth Kentucky Mounted Infantry.