A friend and protégé of Confederate States President Jefferson Davis, he was appointed commander of the Trans-Mississippi Department but failed in his key task, which was to defend the Confederacy's hold on the Mississippi.

[2][3] After a failed attempt at plantation managing, Holmes asked his father for an appointment to the United States Military Academy, from which he graduated in 1829.

[1] I, who knew [Holmes] from his school-boy days, who served with him in garrison and in field, and with pride watched him as he gallantly led a storming party up a rocky height at Monterey, and was intimately acquainted with his whole career during our sectional war, bear willing testimony to the purity, self-abnegation, generosity, fidelity and gallantry, which characterized him as a man and a soldier.

[3] During the Peninsula Campaign in the spring of 1862, Holmes was moved to the Richmond area to defend it from the U.S. assault on the Confederate capital; thus, he became temporarily attached to the Army of Northern Virginia.

His force was repulsed at Turkey Bridge by artillery fire from Malvern Hill and by the U.S. gunboats Galena and Aroostook on the James.

In truth, the entire Confederate counterattack in the Seven Days Battles had been handled ineffectively, and many generals were to blame, including Lee himself.

Nonetheless, his age and unremarkable record in the war up to that point were factors against him, and Lee quickly made it clear that Holmes would not make the cut during the post-Seven Days restructuring of the army.

[4] During his time as commander of the Trans-Mississippi Department, Holmes failed to perform his most important duty: defend the Confederacy's hold on the Mississippi River.

For the most part, the soldiers had no shoes, no uniforms, no munitions, no training, organization, or discipline, a situation worsened by the fact that many communities in Arkansas had no government above the village level.

People did not pay taxes or have any written laws and strongly resisted any attempt to impose an outside government or military discipline on them.

In this situation, Holmes wrote to Richmond that if, by some miracle, he could organize the Arkansas militia into an army and get them across the Mississippi River, they would desert as soon as they got to the east bank.

[7][page needed] After numerous complaints were sent to Davis, who had little understanding of events in a region almost 900 miles from Richmond, Holmes was relieved as head of the Trans-Mississippi Department in March 1863.

On July 4, the day Vicksburg fell to U.S. General Ulysses Grant's army, Holmes attacked the U.S. garrison at Helena, Arkansas with 8,000 men.

He planned a coordinated attack in conjunction with Sterling Price, John S. Marmaduke, James Fleming Fagan, and Governor of Arkansas Harris Flanagin.

In a letter sent to Jefferson Davis on January 29, 1864, Kirby Smith reported that Holmes's age was catching up to him and that he was deficient in energy and suffering memory problems; thus, he needed to be replaced by a younger man.