Burbridge was commissioned as a colonel in the 26th Kentucky Infantry in August 1861. He participated in the Battle of Shiloh, and later, in their attack on Arkansas Post and in the Vicksburg campaign. In 1864, he took command of the District of Kentucky was eventually given a brevet as a major general in July for his defense against an invasion of the state by Union general J.H. Morgan. However, he was subsequently forced to resign his commission due to his involvement in a series of attacks against civilians.