Leiper's Fork is located along the Natchez Trace, which was an important travel route for Native Americans and early European-American settlers. The area was settled in the late 1700s by settlers from North Carolina and Virginia who had received land grants as payment for service in the American Revolution. Colonel Jesse Steed received a land grant of 2,504 acres that includes the site of the village. He sold the area to Jesse Benton, who established a homestead. His son, Thomas Hart Benton, who later was to become U.S. Senator from Missouri, moved the family there in 1801 after his father's death. Natchez Trace travelers called the community around the Benton homestead Bentontown, but over time the area came to be called Hillsboro.

In 1818, a post office was established in the community. Apparently the Hillsboro name was already in use for a community in Coffee County, so the post office was given the name of Leiper's Fork for the stream that runs through the village. The namesake of Leiper's Fork creek was one of two brothers: Hugh Leiper, who completed an early land survey in the area, or Captain James Leiper, who died in the Battle of the Bluffs at Fort Nashborough in 1781.

Growth of the village was stimulated by traffic on the Natchez Trace. Largely as a result of its transportation access, Leiper's Fork was historically the center of trade for western Williamson County and the center of religious and social activities in the area.

The Leiper's Fork post office operated until 1918.