An important potential consequence of climate change is the modification of the water cycle in agricultural areas, such as the American Midwest. Soil moisture is the integrand of the water cycle, reflecting dynamics of precipitation, evapotranspiration, and runoff in space and time, and a key determinant of yield. Here we present projected changes in the hydrologic cycle over a representative area of the American Midwest from regional climate model experiments that sample a range of model configurations. While significant summer soil moisture drying is predicted in some ensemble members, others predict soil moisture wetting, with the sign of soil moisture response strongly influenced by choice of boundary conditions. To resolve the contradictory predictions of soil moisture across ensemble members, we assess an extensive and unique observational data set of the water budget in Illinois. No statistically significant monotonic trends are found in observed soil moisture, precipitation, streamflow, groundwater level, or 2 m air temperature over a recent 26 year period (soil moisture 25 years). Based on this analysis of model simulations and observations, we conclude that the sign of climate change impacts on the regional hydrology of the American Midwest remains uncertain.National Science Foundation (U.S.)