Despite an increasing body of evidence from observed data that climate change is having a significant impact on different types of biogeophysical systems in the Midwest and Great Lakes region, there still remain critical questions of how quickly and how much climate will be altered over this region in the future. For this evaluation, we make use of 31 global climate model (GCM) projections from the Coupled Model Intercomparison Project, Phase 5 (CMIP5). Based on changes in temperature (T) and precipitation (P) over the Midwest, we selected ten GCM scenarios which (1) simulate historical climate well and (2) successfully capture the range of future climate from the entire CMIP5 ensemble. We then downscaled T and P projections to 1/16° gridded data sets for two different emission scenarios (RCP4.5 and RCP8.5) for three 30-year future periods using the Hybrid Delta (HD) statistical downscaling approach which was proven to be applicable for daily-scale application by a validation work using historical data. T is projected to increase across all seasons, with ensemble mean changes up to 6.5 °C by 2100 for the RCP8.5 scenarios. P increases up to 30% in spring and winter with decreasing snowfall to precipitation ratio, while summer P decreases moderately (−15%) by the 2080s. Changes in daily extreme events show similar seasonal patterns including increasing daily extreme P events in winter and decreasing P in summer. Growing season P may actually increase, however, despite projected P reductions in the warmest summer months. Regional warming results in decreased heating degree days (−1639 °C days, −32%) and increasing cooling degree days (+318 °C days, +957%) by 2080s, with overall net reductions in energy demand.