Schofield initially served as a recruiter for Missouri before accepting a position as major of the 1st Missouri Infantry. He served as chief of staff for General Nathaniel Lyon at the Battle of Wilson's Creek. In 1861, he received a promotion to brigadier general. In 1862, he received a promotion to major general. In the Atlanta campaign, he served in command of the XXIII Corps of the Army of the Ohio. He later distinguished himself at the Battle of Franklin, in Tennessee. In 1864, he became the commander of the Department of North Carolina. He served in this position until the end of the war.