At the outbreak of the war, McPherson joined the United States Army. He was soon promoted to the rank of lieutenant colonel to serve as aide de Camp to General Henry Halleck in the Department of Missouri. By August 1861, McPherson was serving as a first lieutenant of engineers. In February 1862, he became chief engineer under Ulysses Grant. McPherson played an important role in the capture of Fort Henry, Fort Donelson and Corinth. In October 1862, he was promoted to major general as commander of commanded the 2nd division of the Army of Tennessee. McPherson served in this capacity through the Vicksburg Campaign. He was killed in the Battle of Atlanta on July 22, 1864.
