Cahokia Mounds, one of UNESCO's World Heritage Sites, was first inhabited around 700 AD and continued until about 1400 AD. These prehistoric Indians created the most sophisticated early civilization north of Mexico. Cahokia's occupants developed an agricultural system focused on corn, squash, and oily seed plants. This combined with hunting, fishing, and gathering wild foods enabled the community to develop a highly specialized and complex social, political, and religious organization.

Cahokia covered nearly 6 square miles and had a peak population of about 20,000 arranged in residential areas, plazas, and courtyards in and around a central stokade. Originally there were about 120 mounds, though the locations of only 109 are recorded. Many have been lost to farming or urban construction. The mounds were used for siting of houses for the elite, for burials, and for directional purposes. An estimated 50 million cubic feet of earth was moved, basket by basket, to construct the mounds. A circular area of cedar posts ("Woodhenge") apparently identified progress of the calendar year.

The end of Cahokia is presumed due to depletion of resources (food and wood) and possibly climate change. The city began to decline around 1200 and was abandoned around 1400. Where the inhabitants went is unknown.