After organization and muster, the regiment moved north into Kentucky and camped at Bowling Green, where it remained until early 1862. The 4th Kentucky Infantry first saw combat at the Battle of Shiloh in April 1862, losing 49% of its strength in the two-day battle. The regiment fell back to Corinth, Mississippi, after the battle and was next ordered to Vicksburg, Mississippi, to aid in the city's defense. The 4th Kentucky soon received orders to reinforce General Braxton Bragg, whose troops were engaged in the Kentucky Campaign. The regiment was north of Knoxville, Tennessee, 20 miles from Cumberland Gap, when it received orders to return to Murfreesboro, Tennessee, because of Bragg's subsequent retreat after the Battle of Perryville on October 8, 1862.