Millersburg, located in the center of Holmes County was named in honor of Charles Miller. In 1815 Miller  laid out lots to establish a small village that was later to become the county seat. The first building was a tavern built in 1819. A year later, a log cabin school house was constructed and in 1821 a typical frontier store was completed.

During the winter of 1820 -21, the first religious services were believed to be held in the school. A log courthouse, the first of three, was built in 1825 and by 1834 there were about sixty buildings and a population of nearly 300 persons. In 1833, Millersburg contained ten stores, four taverns, four practicing physicians, three attorneys, one printing office, one meeting house, one apothecary's shop, and 73 dwelling houses

Millersburg was incorporated February 17, 1835.