John Wesley Smith was born around 1839 in South Carolina to William and Elizabeth Smith. His father was a farmer who owned $1,200 of real estate by 1850. He grew up and attended school in Marlboro District, South Carolina, and his father died in 1858.
He enlisted in the Confederate army on April 13, 1861, and he mustered in as a sergeant in Company K of the 8th South Carolina Infantry. He expressed devotion to the Confederate cause. In October 1861, he wrote that it "is true that we who have volunteered have to undergo many hardships but if we get back safe from the wars we will have our reward in the gratitude of a grateful people. I could never stay at home and leave my friends and others to fight the battle of independence alone while I was enjoying myself at home. I should feel that I could be justly accused of cowardice." Later that month, he added that the "soldiers of the Confederate States are fighting for life home liberty, all that is dear to them."
He fell ill in the summer of 1861 and spent several months recovering at home. He rejoined the regiment sometime in 1862. His health deteriorated again that fall, and he spent several months at a hospital in Lynchburg, Virginia. He was reduced to the ranks in April 1863, and Confederates assigned him to work as a clerk on the examining board. He later became a hospital clerk in Richmond, Virginia. Union forces captured him in Richmond on April 3, 1865, and he received a parole on April 24, 1865.
He returned to Red Hill, South Carolina, after the war, and he earned a living as a lawyer. He later worked as a custom house clerk. In November 1916, he applied for admission to the Confederate Infirmary in Columbia, South Carolina. He died on November 21, 1917.