Six high-resolution climatic reconstructions, based on diatom analyses from lake sediment cores from the northern prairies of North America, show that shifts in drought conditions on decadal through multicentennial scales have prevailed in this region for at least the last two millennia. The predominant broad-scale pattern seen at all sites is a major shift in moisture regimes from wet to dry, or vice versa (depending on location), that occurred after a period of relative stability. These large-scale shifts at the different sites exhibit spatial coherence at regional scales. The three Canadian sites record this abrupt shift between anno Domini 500 and 800, and subsequently conditions become increasingly variable. All three U.S. sites underwent a pronounced change, but the timing of this change is between anno Domini 1000 and 1300, thus later than in all of the Canadian sites. The mechanisms behind these patterns are poorly understood, but they are likely related to changes in the shape and location of the jet stream and associated storm tracks. If the patterns seen at these sites are representative of the region, this observed pattern can have huge implications for future water availability in this region.