The Division was organized on October 16, 1863, to consist of the Departments of the Ohio, the Tennessee, and the Cumberland, which embraced all of the Union armies stationed between the Mississippi River and the Appalachian Mountains.
On April 19, 1865, the portions of the Department of North Carolina that were not occupied by William T. Sherman at the time were transferred to the Military Division of the James.
The Division of the Mississippi was victorious at the Battle of Chattanooga in November 1863, effectively routing the Confederate armies in Tennessee.
When General Grant was called East by Lincoln to command all the Union armies, he was succeeded as head of the Division by Maj. Gen. William Tecumseh Sherman.
Under Sherman, the Division invaded the state of Georgia, capturing Atlanta in September 1864 and then marching to the port of Savannah.