Waynesboro owes its existence to the railroad that was constructed through Wayne County in 1854. The Mobile and Ohio Railroad established stations roughly every five to six miles along its line, and a station was built roughly five miles north of Winchester, which was an established and thriving community at the time, and was named Waynesboro.
The town of Waynesboro was laid out around the train stop and property was offered for sale by the railroad. By 1860, some 15 to 20 families called Waynesboro home, and businesses gradually began springing up to meet the needs of people living in the area.
By 1876, the town was granted a charter of incorporation by the state, and became the county seat of government. Hotels sprang up and several general stores were open for business. A school and at least two churches were also established around this time.
A new brick courthouse was constructed in 1892, replacing a structure that was destroyed by fire. It would ultimately stand until being replaced in 1935 and would be torn down in 1958.
The turn of the 20th Century saw Waynesboro's stature continue to grow as a hub for commercial activity. As the population steadily grew in those early years, roads were improved and residential areas began to spring up on both sides of the railroad.
More stores would open as the years went by, including more general stores, drug stores, a bank, a United States Post Office, hotels and taverns, a livery stable, blacksmith shops and a newspaper office. A sawmill and brick factory also came into existence.