On the May 30, 1861, the regiment left Indianapolis, by way of Cincinnati, Ohio, for Grafton, Virginia (now West Virginia). Sent on to the town of Webster, they arrived on June 2 and marched that same night to Philippi. On the morning of June 3, the 6th Indiana participated in the Battle of Philippi, one of the first land battles of the Civil War. They later participated in the Rich Mountain Campaign.