Abstract Baseflow is an essential water resource because it is the groundwater discharged to streams and represents long-term storage. Understanding its future changes is a major concern for water supply and ecosystem health. This study examines the impacts of climate and agriculture on monthly baseflow in the U.S. Midwest through the end of the 21st century. We use a statistical approach to evaluate three scenarios. The first scenario is based on downscaled and bias corrected global climate model (GCM) outputs and the representative concentration pathway (RCP) 8.5, and agriculture is held constant (and equal to the mean from 2013 to 2019). In the next two scenarios, climate is held constant (2010–2019) to isolate the impact of agriculture on baseflow. In terms of agricultural changes, we consider scenarios representative of either increases or decreases with respect to the production of corn and soybeans. Changes in the climate system point to increases in baseflow that are likely a result of increased precipitation and antecedent wetness. Seasonally, warmer temperature in the winter and spring (i.e., February to July) is expected to cause increasing trends in baseflow. Changes in land use showed that agriculture would either mitigate the impact of climate change or possibly amplify it. Expanding corn and soybean areas would increase baseflow in the Corn Belt region. On the other hand, converting land back to perennial vegetation would decrease baseflow throughout the entire year. Despite its simplicity, this study can provide basic information to understand where to expect adverse effects on baseflow and thus improve land management practices in those areas.