In 1829 a little town in Liberty Township was named Clayville, honoring Henry Clay, the Kentucky statesman. In 1835, Clayville consisted of ten houses and 43 people. The Town of Clayville was platted in 1851 by George Washington Wills. However, the name was changed to Clayton in 1858 because another Clayville already existed in Dubois County.
The first two houses in Clayton were built by Thomas Potts and Lewis T. Pounds, and Parker & Foote was the first store. George Wills built the first hotel and John Miles and James Worrell developed the first flouring mill. The first train passed through in 1852. By the early 1900's, the town had electric service, supplied by the Danville Light, Heat and Power Co.
The first schoolhouse built in Clayton was erected in 1867. In the spring of 1868, Howard Mitchell started a subscription school in the new building. It was not unitl 1897 the first high school of the township was built in Cartersburg. In the fall of 1901 the high school was transferred to Clayton, which made it nearer the middle of the township and the center of the school population.
In 1909 the town was incorporated and had a population of 497. An excerpt from a Hendricks County Historical Periodical in 1910 accounts that "Clayton of today is a prosperous, progressive and beautiful little city. Trade is excellent among the business houses and social life of the town is of high standard. Good communication is available by way of the railroad or interurban to the capital city and other towns in the southern part of the county." An essay by Louise Overton in 1930 described the town as "a beautiful and well cared for little city. In addition to three grocery stores, there are three garages, a Post Office, two barber shops, three beauty shops, two restaurants, two hardware stores, one mill, one drug store, two doctors, one meat shop, one shoe shop and one poultry house."