William Isbell was born in July 1837 in Amherst County, Virginia, to Robert Isbell and Angelina Boaz. His father was a merchant and farmer who owned $5,000 of real estate and $8,460 of personal property by 1860. Isbell grew up and attended school in Appomattox County, Virginia, and by 1860, he was working as an overseer. President James Buchanan appointed him postmaster of Stonewall Mills in Appomattox County on June 8, 1860.
He enlisted in the Confederate army on May 1, 1861, and he mustered in as a private in Company A of the 44th Virginia Infantry later that day. According to his service records, he was 5 feet, 11½ inches tall, with brown hair and blue eyes. He was promoted to sergeant on December 28, 1861, and he was transferred to the 20th Virginia Heavy Artillery Battalion on March 27, 1862. He expressed devotion to the Confederate cause, writing in July 1861 that he believed the "cause which I have espoused to be just & holy" and that he was "willing to suffer & die in its defence."
The battalion was stationed in Richmond for most of the war, and the men took part in the Appomattox campaign. He was probably captured during the Appomattox Campaign, and he spent the next two months imprisoned at Point Lookout, Maryland. He swore an oath of allegiance to the United States government on June 14, 1865.
Isbell returned to Stonewall, Virginia, after the war and earned a living as a ferryman. By 1900, he was living with his brothers and sisters in Stonewall and working as a farmer. He died of heart disease, possibly brought on by an opium addiction, in Stonewall on November 14, 1924.