During the American Civil War, he entered the Union Army with a commission as brigadier general of volunteers. He first organized the northern Kentucky defenses around Cincinnati. He commanded the Department of the Ohio from September to November 1861. During this time, he conspired with espionage agent James J. Andrews on plans to steal a train in Georgia and disrupt a railroad vital to the Confederate States Army coincident with Mitchel's planned attack on Chattanooga, Tennessee. The raid failed, as did Mitchel's military operation. Andrews and a number of his men were captured. Andrews himself was among eight men who were tried in Chattanooga. They were hanged in Atlanta by Confederate forces, but were later buried in the National Cemetery at Chattanooga in 1887.