Claysville was one of the original pike towns along the National Road. In 1817, early settler and landowner John Purviance learned that the new road being built between Cumberland, Maryland, and Wheeling, Virginia, would cross his land, and he platted a town there, naming it for U.S. Senator Henry Clay, whose support for public improvements included the National Road. As the first interstate highway built by the federal government and the first constructed highway to cross the mountains, the road brought traffic, westward migration, freight hauling, and access to eastern markets for local farmers after its completion to Wheeling by 1818. Claysville became an important stopping point where taverns and inns served wagon drivers, livestock drovers, and other travelers, and the town grew quickly, opening its first school in 1818 and building a Presbyterian Church in 1820. Many early settlers were of Scots-Irish descent, and many road workers were also Irish. Incorporated as a borough in 1832, Claysville had 275 residents by 1850. The arrival of the railroad in 1856 began the decline of the National Road, but Claysville continued to grow because it stood on two major transportation links and served as a regional agricultural center. An oil and gas boom in the late 1800s further increased its prosperity, diversified its businesses, and raised its population to 856 by 1900. In 1908, the town had 10 stores, three restaurants, two furniture dealers, two livery stables, a carriage shop, six physicians, two hotels, two banks, and two lumber mills. The Claysville Flour Mill produced three brands of flour, and George Sprowls ran a hardware business large enough to require nine buildings. Claysville was also connected to notable figures: Henry Clay, for whom it was named; Benjamin Franklin Jones, born near Claysville in 1824, who later co-founded the Jones and Laughlin Steel Company; and William Holmes McGuffy, born near the present borough in 1800, whose McGuffy Readers became the most popular reading textbooks of the 19th century.