The Customs House Museum & Cultural Center is partially housed in a historic 1898 building, which was originally constructed as a Federal Post Office and Customs House to handle the large volume of foreign mail created by the city’s international trade in tobacco. It also housed the Clarksville Department of Electricity from 1940 to 1983 before becoming a museum. The building was placed on the National Register of Historic Places in 1972.

With its 1983 charter, this institution was founded as the Clarksville-Montgomery County Historical Museum. The museum’s mission and building expanded in 1996. The institution became known as the Customs House Museum & Cultural Center.