With the outbreak of the Civil War, Walker was commissioned colonel of the 40th Tennessee Volunteer Infantry on November 11, 1861.

Walker was commissioned brigadier general on March 11, 1862, and was posted at Kentucky Bend, with the command of the 40th Tennessee falling to Lt. Col. C. C. Henderson.

Being forced to surrender at Island Number 10, Walker was exchanged and rejoined the army at Corinth, Mississippi, before it retreated to Tupelo.

He was reassigned to the Trans-Mississippi Department on March 23, 1863, commanding a brigade of cavalry under Lt. Gen. Theophilus Holmes at the Battle of Helena.

"I have not pronounced you a coward," Marmaduke wrote, "but I desire to inform you that your conduct as commander of the cavalry was such that I determined no longer to serve you."

At dawn on Sunday, September 6, Walker and Marmaduke squared off with Colt 1851 Navy Revolvers on the north bank of the Arkansas River near Little Rock.