This research examines and compares the distributions of archaeological sites and materials in order to investigate native settlement patterns and resources use throughout 12,000 years of prehistory and protohistoric time within the Apalachicola/Lower Chattahoochee River valley of northwest Florida, southwest Georgia, and southeast Alabama. Geographic Information Systems (GIS) are used to map the distributions of sites from different time periods and to explore their relation to various environmental characteristics that are now available in digital format. I employ tools now available in GIS to examine several longstanding research questions and expand upon archaeological interpretations within this region, where the University of South Florida (USF) has an ongoing research program. The results of this work illustrate change through time and space as cultures begin to adapt to post-Pleistocene ecological change, develop food production and complex societies, and react to the appearance of European groups.