The consequences of climate change vary over space and time. Effective studies of human responses to climatically induced environmental change must therefore sample the environmental diversity experienced by specific societies. We reconstruct population histories from A.D. 600 to 1280 in six environmentally distinct portions of the central Mesa Verde region in southwestern Colorado, relating these to climate-driven changes in agricultural potential. In all but one subregion, increases in maize-niche size led to increases in population size. Maize-niche size is also positively correlated with regional estimates of birth rates. High birth rates continued to accompany high population levels even as productive conditions declined in the A.D. 1200s. We reconstruct prominent imbalances between the maize-niche size and population densities in two subregions from A.D. 1140 to 1180 and from A.D. 1225 to 1260. We propose that human responses in those subregions, beginning by the mid-A.D. 1200s, contributed to violence and social collapse across the entire society. Our findings are relevant to discussions of how climate change will affect contemporary societies.