He served as a brigadier general under Stonewall Jackson and James Longstreet, before commanding the Texas Division unit in the Trans-Mississippi Department, known as Walker's Greyhounds for their speed and agility.

Walker joined the United States Army as a first lieutenant of the Regiment of Mounted Rifles in 1846, and served with distinction in the Mexican–American War, where he was breveted to captain for San Juan de los Llanos and was wounded at Molino del Rey.

His division occupied Loudoun Heights, overlooking Harpers Ferry, West Virginia before its garrison surrendered to Stonewall Jackson on September 15, 1862.

In November 1862, Walker was promoted to major general and transferred to the Trans-Mississippi Department, where he was given command of 12 Texas regiments, numbering 12,000 men, training at Camp Nelson in Arkansas.

In March 1863, the new commander of the Trans-Mississippi Department, Lt. Gen. Edmund Kirby-Smith, assigned the Greyhounds to Maj. Gen. Richard Taylor's Western Louisiana command, and they were given the task of attacking Maj. Gen. Ulysses S. Grant's supply line that ran on the western bank of the Mississippi River on the Louisiana side opposite the besieged Vicksburg, Mississippi.

Grant, having recently moved his supply lines to the eastern banks of the Mississippi, was not harmed by the attack of Walker's Greyhounds.

The troops fought bravely, but poorly trained, suffered heavy casualties at the hands of Walker's men.

Walker spent the balance of the summer fruitlessly patrolling the northeastern area of Louisiana, unable to cross the Mississippi and support the besieged Vicksburg.

Walker engaged Steele at the Battle of Jenkins' Ferry on April 30, 1864, about 30 miles south of Little Rock, Arkansas.