Dietary reconstruction using carbon and nitrogen stable isotopes from archaeological human bone samples from coastal Georgia and northern and Gulf Coast Florida dating between 400 B.C. and A.D. 1700 serves to illustrate the complexity of the agricultural transition in that region. Isotope analysis of 185 collagen samples drawn from early prehistoric, late prehistoric, and contact-period mortuary sites encompasses two major adaptive shifts in the region, namely the adoption of maize agriculture in late prehistory and the increased emphasis on maize during the mission period. Prior to European contact—and especially before the establishment of Spanish missions among the Guale, Yamasee, Timucua, and Apalachee tribal groups—diet was strongly influenced by local environmental factors. Before contact, coastal and inland populations had different patterns of food consumption, as did populations living in Georgia and Florida. Coastal populations consumed more marine and less terrestrial foods than inland populations. In general, maize was adopted during the eleventh century A.D. by virtually all Georgia populations. However, with the exception of the Lake Jackson site, a major Mississippian center in northern Florida, Florida populations show little use of maize before contact. Following European contact, maize became wide-spread, regardless of location or habitat within the broad region of Spanish Florida. Missionization appears to have been an important factor in the convergence of native diets toward agriculture and away from foraging. This increased emphasis on maize contributed to a decline in quality of life for native populations.