It's a pretty tall order to quickly summarize tens of thousands of years of human occupation on an entire continent, so instead I'll refer you to a set of posts I made a couple months back. It hits some of the archaeological highlights from the Ohio Valley from the Ice Age to the arrival of Europeans.

Skimming through it now, I did notice that at least one thing I said there has since become out-dated. The Adena are listed as having lasted until 2100 BP, but in January of this year new data was announced that shows they were still active 140 years later than previously thought.