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Recently, researchers investigating the origins of domestication have debated the significance of resource intensification in the shift from foraging to food production. In eastern North America, one of several independent centers of domestication, this question remains open. To determine whether initial domestication may have been preceded by intensification in eastern North America at approximately 5000 cal BP, I evaluated the archaeofaunal assemblages from six sites in the middle Tennessee River valley. Analyses of these data suggest that overall foraging efficiency gradually declined prior to initial domestication, but patch-specific declines in foraging efficiency occurred in wetland habitats and not terrestrial ones. Climatic warming and drying during the Middle Holocene, growing human populations, and oak-hickory forest expansion were the likely drivers of these changes in foraging efficiency. These results support the hypothesis that initial domestication in eastern North America was an outcome of intensification driven by environmental change and human population increases. Finally, while the debate concerning the relationship of intensification to domestication has been framed in terms of a conflict between niche construction theory and optimal foraging theory, these perspectives are compatible and should be integrated to understand domestication more fully.