Impacts of climate change on watershed hydrology are subtle compared to cycles of drought and surplus precipitation (PPT), and difficult to separate from effects of land-use change. In the US Midwest, increasing baseflow has been more attributed to increased annual cropping than climate change. The agricultural changes have led to increased fertilizer use and nutrient losses, contributing to Gulf of Mexico hypoxia. In a 25-yr, small-watershed experiment in Iowa, when annual hydrologic budgets were accrued between droughts, a coupled water-energy budget (ecohydrologic) analysis showed effects of tillage and climate on hydrology could be distinguished. The fraction of PPT discharged increased with conservation tillage and time. However, unsatisfied evaporative demand (PET - Hargreaves method) increased under conservation tillage, but decreased with time. A conceptual model was developed and a similar analysis conducted on long-term (>1920s) records from four large, agricultural Midwest watersheds underlain by fine-grained tills. At least three of four watersheds showed decreases in PET, and increases in PPT, discharge, baseflow and PPT:PET ratios (p < 0.10). An analysis of covariance showed the fraction of precipitation discharged increased, while unsatisfied evaporative demand decreased with time among the four watersheds (p < 0.001). Within watersheds, agricultural changes were associated with ecohydrologic shifts that affected timing and significance, but not direction, of these trends. Thus, an ecohydrologic concept derived from small-watershed research, when regionally applied, suggests climate change has increased discharge from Midwest watersheds, especially since the 1970s. By inference, climate change has increased susceptibility of nutrients to water transport, exacerbating Gulf of Mexico hypoxia.