The first European settlement in the vicinity of present-day Clay City was in 1786, by Stephen Collins and his brother, after their discovery of pyrite deposits. Shortly afterwards, the brothers set up the first iron forge west of the Allegheny Mountains and established Collins Forge. The Collins brother sold their forge to Clark and Smith in 1805, the forerunner company of the Red River Iron Works. For much of the 19th century, the settlement was known by the same name as the forge. By the 1880s, the post office was moved across the river and was renamed Waltersville for the local family carrying the same surname.

By 1883 the settlement was named Clay City, possibly for the local clay deposits. It is believed that the name was officially changed from Waltersville on August 13, 1883, when the post office was renamed Clay City. The settlement was incorporated as a fifth-class city on April 19, 1890.