In rethinking the ontological bases of pre-Columbian North America, water emerges as the primary substance through which people lived their histories. Simplistic climate change and flood-event scenarios aside, the atmospheric water cycle enmeshed peoples in ways that explain Mississippi Valley agriculture, astronomy, religious practice, political development, and historical ties to Mesoamerica. The linchpin of such arguments is the greater Cahokia phenomenon (AD 1000s-1300s). Beginning with new large-scale archaeological excavations and a refined chronology in that region, I trace water-human relationships through local-to-continent-wide genealogies of maize cultivation, mussel shell use, and American Indian sweat lodges and other “water shrines.” There are theoretical implications for how we understand history and humanity.