The companies of the 4th regiment were assembled in August, 1861, initially for state service, with an original strength of 787 men.

During the Battle of Port Gibson, General William Edwin Baldwin wrote that, "The Fourth Mississippi, Lieutenant-Colonel Adaire, [was] so posted as to bear the severest part of the conflict".

[3] The regiment was captured for a second time when the Confederate garrison at Vicksburg surrendered to Union forces on July 4, 1863.

After being exchanged, the 4th was sent to Tennessee in the fall of 1863 to reinforce the troops under General Braxton Bragg who were fighting at Chattanooga, but arrived too late to take part in the battle, instead remaining in camp in north Georgia.

The remnants of the 4th Regiment were then captured after the Battle of Fort Blakeley in Alabama on April 9, 1865, shortly before the final Confederate surrender.