Cheatham joined the Confederate States Army as a brigadier general on May 9, 1861, and became a brigade commander in the Western District of Department Number Two, under Maj. Gen. Leonidas Polk. His first test in the war was in Missouri on November 7 at the Battle of Belmont, leading three regiments in Brig. Gen. Gideon J. Pillow's division against Union Brig. Gen. Ulysses S. Grant, also in his first Civil War combat. In December, Cheatham and his division received the Thanks of Congress, "for the desperate courage they exhibited in sustaining for several hours, and under most disadvantageous circumstances an attack by a force of the enemy greatly superior to their own, both in numbers and appointments; and for the skill and gallantry by which they converted what at first threatened so much disaster, into a triumphant victory."
Cheatham was promoted to major general, on March 10, 1862, and was appointed commander of the 2nd Division, First Corps, Army of Mississippi. He led his division at the Battle of Shiloh and was wounded, although it is unclear whether this occurred on April 6 or April 7, 1862. General Braxton Bragg became commander of the Army (soon to be designated the Army of Tennessee) and Cheatham served under him at Perryville and Stones River. At the latter battle, Cheatham performed sluggishly, ordering piecemeal assaults; observers claimed he had been drinking heavily and was unable to command his units effectively.
Cheatham continued as a division commander under Bragg at the Battle of Chickamauga and, following that rare Confederate victory in the West, was elevated to corps command on September 29, 1863. He was on the right flank of Missionary Ridge when Bragg was defeated by Grant at Chattanooga, engaged to block the Union Army in the final hours of the battle.
In 1864, Cheatham fought well in the Atlanta Campaign under General Joseph E. Johnston, and later Lt. Gen. John Bell Hood, inflicting heavy casualties on William T. Sherman's Union Army at the Battle of Kennesaw Mountain, and being wounded at the Battle of Ezra Church. He was in corps command for the battles around Atlanta, replacing William J. Hardee, who had resigned when Hood took command.
Cheatham's most famous service came as a corps commander under Hood in the Franklin-Nashville Campaign. He was engaged in all the major battles of the campaign, receiving notoriety when the Union Army under Maj. Gen. John M. Schofield was able to slip by him and escape from the Battle of Spring Hill, which foiled Hood's plan and led to the disastrous Confederate defeat at Franklin. Hood accused Cheatham of dereliction of duty and the enmity between them lasted for the rest of their lives. After the collapse of Hood's army at Nashville, Cheatham rejoined Johnston's army for the Carolinas Campaign (as a division commander, the highest position this small army could justify), surrendering to General Sherman in North Carolina in April 1865.
