In this study, we have integrated a suite of Holocene paleoclimatic proxies with mathematical modeling in an attempt to obtain a comprehensive picture of how watersheds respond to past climate change. A three-dimensional surface-water–groundwater model was developed to assess the effects of mid-Holocene climate change on water resources within the Crow Wing Watershed, Upper Mississippi Basin in north central Minnesota. The model was first calibrated to a 50 yr historical record of average annual surface-water discharge, monthly ground-water levels, and lake-level fluctuations. The model was able to reproduce reasonably well long-term historical records (1949–1999) of water-table and lake-level fluctuations across the watershed as well as stream discharge near the watershed outlet. The calibrated model was then used to reproduce paleo-groundwater and lake levels using climate reconstructions based on pollen-transfer functions from Williams Lake just outside the watershed. Computed declines in mid-Holocene lake levels for two lakes at opposite ends of the watershed were between 6 and 18 m. Simulated streamflow near the outlet of the watershed decreased to 70% of modern average annual discharge after ∼200 yr. The area covered by wetlands for the entire watershed was reduced by ∼16%. The mid-Holocene hydrologic changes indicated by these model results and corroborated by several lake-core records across the Crow Wing Watershed may serve as a useful proxy of the hydrologic response to future warm, dry climatic forecasts (ca. 2050) made by some atmospheric general-circulation models for the glaciated Midwestern United States.