In the rugged uplands of eastern Kentucky, archaeological evidence of pre-maize plant cultivation is largely absent from stream bottom locations, being concentrated instead within upland rockshelters. Some researchers have hypothesized that the apparent failure of early food producers to exploit rich bottomland soils was an economically sound response to the shortcomings of local stream valley habitats. Instead, seed crop farmers favored hillsides and ridgetops, which were less costly to clear and maintain under cultivation than narrow and densely vegetated stream bottoms. We analyze the goodness of fit between hypothetical upland and lowland cultivation systems and new evidence for human interaction with plant communities and the agricultural potential of soils. Seed and wood assemblages indicate a temporal association between increased human interaction with lowland plant communities, higher levels of habitat disturbance, and greater reliance on cultivated plants. However, there is no convincing evidence that plant cultivation caused disturbance and exploitation of lowlands. Expansion of mesic and hydric habitats was in part a response to increased precipitation and frequency and severity of flooding. Floodplains became largely unsuitable for human habitation, contributing to more intensive exploitation of uplands. While ridgetops and steep slopes were both poor locations for cultivated plots, other upland soils on limestone benches also had good agricultural potential, as did the soils on lower colluvial slopes.