Before railroads, many historically significant cities in the US formed near the mouth of rivers (New York, New Orleans), or the confluence of two or more rivers (St. Louis, Pittsburgh). These locations were due to their natural ability to control trade and transportation. Cairo, IL sits at the confluence of the Ohio and the Mississippi, the two largest rivers by volume in the US. The watersheds of these rivers upriver of Cairo contains almost the entirety of the farmland in the Midwest. Moreover, geographically and culturally the city sits in a very central location of the US frontier in the early 1800's. It is the most southern town in the "North".

In reality, this town is very insignificant, both in the past and the present. It wasn't even permanently established until 1862. So, r/askhistorians, can you please explain why Cairo is a backwater town that never had its day, while New Orleans, St. Louis and (especially) Memphis became great river towns?