Ancient cultural changes have often been linked to abrupt climatic events, but the potential that climate can exert a persistent influence on human populations has been debated. Here, independent population, temperature, and moisture history reconstructions from the Bighorn Basin in Wyoming (United States) show a clear quantitative relationship spanning 13 ka, which explains five major periods of population growth/decline and ~45% of the population variance. A persistent ~300-y lag in the human demographic response conforms with either slow (~0.3%) intrinsic annual population growth rates or a lag in the environmental carrying capacity, but in either case, the population continuously adjusted to changing environmental conditions.