Founded in 1857 by Robert Wilson, Louisville was originally known as Rock Post. The area was once part of the Potawatomi Hunting grounds and a large majority of the settlers were either associated with the Pottawatomie Indian Reservation or commerce on the Oregon Trail. Louisville was named for Robert Wilson’s son, Louis, and for Louis Vieux, a successful businessman in the area. The town was a contender for county seat of Pottawatomie County but lost to St. George in 1861 and Westmoreland in 1882.

On November 8, 1875, Louisville was struck by an earthquake. In 1882, with the county seat in Westmoreland and the Union Pacific Railroad built through Wamego, the town’s population swiftly declined.

About three miles east of Louisville was the Vermillion Crossing of the Oregon Trail operated by Louis Vieux. Vieux is buried in the Vieux Family Cemetery on top of a hill. Nearby, on the banks of the river, is a cholera cemetery from 1849, which is estimated to contain at least fifty graves, although only two stones —both native sandstones —remain. The Louis Vieux Elm Tree is across the river and is estimated to be over 300 years old. The tree had been afflicted with Dutch Elm disease, a lightning strike and vandalism and efforts were taken to protect and shelter the tree’s stump. In August 2011, the stump was destroyed by fire. Near the tree are the graves of seven unknown soldiers.