Lewisport was originally a ferry landing site known as "Little Yellow Banks", in allusion to Owensboro's original name of "Yellow Banks". The first settler was James Prentis, who platted the current town in 1837 with his brother John. An attempt to rename the city "Prentisport" failed, though, when James insisted the town be named after his friend Dr. John Lewis instead. The town was chartered as "Lewisport" in 1839, and the post office was established under that name in 1844. The city was formally incorporated by the state assembly the same year, but needed to be reincorporated in 1882.