This paper examines the archaeological and biological evidence for shifts in human subsistence strategies during the transition from hunting and foraging to maize agriculture as posited in the Río Balsas, or lowland origin of maize, model and the Tehuacán, or highland origin of maize, model. These are two different interpretations of the genetic evidence for the ancestry of maize, the archaeological evidence for plant exploitation, and the ecological evidence for paleoenvironments and climate change in the two regions. In contrast to Panama, where there is good evidence for progressive intensification of human forest disturbance by 10,000 B.P., horticultural forest clearing by 8000 B.P., and slash-and-burn agriculture by 6000 B.P., the evidence for Mesoamerica, where maize agriculture originated, fits a different picture of biocultural evolution. The lowland regions of Mexico, Guatemala, Belize, and probably Honduras, were apparently undisturbed, semi-evergreen forests around 10,000 B.P. New findings from experimental maize genetics, combined with the comprehensive archaeological picture from Tehucán, Oaxaca, Tamaulipas, and the Valley of Mexico, support a highland Mesoamerican origin of maize.