Clayton and his twin brother, William, were born on a farm near Chester, Pennsylvania to John and Ann Glover Clayton, his father an orchard keeper and carpenter. His parents had ten children in all, although six died in infancy. Clayton had a normal childhood of any boy of the time and went on to marry a woman named Sarah Ann with whom he had six children. During the Civil War, he served in the Army of the Potomac where he engaged in several campaigns in the east. In 1867, he and his family moved to Arkansas where he managed a plantation owned by older brother, Powell Clayton, who would become the Governor of Arkansas the next year.
Clayton remained involved in Arkansas politics in the years after Reconstruction. With the support of blackRepublican voters, he became sheriff of Jefferson County in 1876, being reelected to five successive, two year terms. In 1888, he ran to represent Arkansas's 2nd congressional district in the United States House of Representatives, going up against incumbent DemocratClifton R. Breckinridge. The election became one of the most fraudulent in Arkansas' history. Clayton lost the election by a narrow margin of 846 out of over 34,000 votes cast. However, in one case in Conway County, four masked and armed white men stormed into a predominately black voting precinct and, at gunpoint, stole the ballot box that contained a large majority of votes for Clayton. Losing under such circumstances, Clayton decided to contest the election and went to Plumerville, Arkansas to start an investigation on the matter. On the evening of January 29, 1889, an unknown assailant shot through the window to the room he was staying in at a local boardinghouse and killed him instantly. He was later declared the winner of the election and Breckinridge was unseated and the seat declared vacant. His assassin was never found.
Barnes, Kenneth C. Who Killed John Clayton? Political Violence and the Emergence of the New South, 1861–1893. Durham, N.C.: Duke University Press, 1998.