For more than a decade before Bishopville got its name in honor of Jacques Bishop, it was known as Singleton's Crossroads. The 465 acres of land was granted to Jacob Chamber by the state of South Carolina in 1786. Daniel Carter later purchased the property, and it was again sold to William Singleton in 1790. This was where the name Singleton's Crossroads originated.

The tavern owned by Singleton and his wife sat at the intersection of what was once known as Mecklenburg Road, now named Church Street, and McCallum Ferry Road, now known as Main Street. During that time, the tavern was a stopping place for the stagecoach between Georgetown and Charlotte. (Now, this intersection involves US Highway 15, which was once the premier north-south route from New York to Miami.) In 1798, William Singleton died, leaving his wife owner of the tavern until her death in 1820. One year later, the land was sold to Jacques Bishop. During this time period, the area around present-day Bishopville was said to be composed of mostly wilderness, with only a few scattered, primitive houses.

Although voting for the creation of Lee County and for making Bishopville its country seat occurred in 1892, there was a delay in enacting these votes until February 1902, when it was ruled that Bishopville had met all requirements to be a county seat. This led to the marking of county boundaries, which were along Lynches River, Black River, Scape Ore Swamp, Sparrow Swamp, Long Branch, and Screeches Branch, as well as the development of a courthouse and jail. As surveyed in the parent counties, the main limits followed old roads and artificial limits.

It wasn't until December 15, 1902, that Bishopville received the good news of their success. To celebrate, the town hosted speeches and the shooting of the old cannon many times repeatedly. This same old cannon is located on the concrete base in front of Lee County's Courthouse in Bishopville.

Lee County has historically been a leader in cotton production in the state and is the home of the South Carolina Cotton Museum.