William Clark, of the famous Lewis and Clark expedition, platted a town in 1827 at this northernmost point of what is now the Tennessee Tombigbee Waterway. Once known as the village of Pekin, General Clark renamed this new town in honor of the Padouca Indians, whom Clark referred to as, "once the largest Nation of Indians known in this country, and now almost forgotten."

Local folklore speaks of the legendary Chief Paduke, known for his peaceful leadership of a Chickasaw subtribe that resided in this region. A statue of Chief Paduke can be seen on Jefferson boulevard at 19th Street. A twin of this statue is in a fountain in front of Union Station in Washington D.C. Paducah is the only major city in the Commonwealth of Kentucky with an Indian name.

Paducah's early growth during the 1830’s was due to its strategic location at the conjoining of the Ohio and Tennessee Rivers. Paducah’s river industry was crucial to the growth of the city, and still remains one of the top industries in the area.