The Town of Louisville was established from part of the Town of Massena. It was the eleventh town erected by an Act of the Legislature passed on April 5, 1810. Almost half of Louisville was lost to from the Town of Norfolk in 1844. An attempt to take part of Louisville for the Town of Massena in 1849 was rejected.

Louisville is one of the northern towns of St. Lawrence County now contains 63.8 square miles that is bordered by Massena on the east, Norfolk on the south, Waddington on the west, and the St. Lawrence River on the north. The Grasse River flows across the central part nearly parallel with the St. Lawrence.