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Irrigated agriculture alters near-surface temperature and humidity, which may mask global climate change at the regional scale. However, observational studies of irrigation-induced climate change are lacking in temperate, humid regions throughout North America and Europe. Despite unknown climate impacts, irrigated agriculture is expanding in the Midwest United States, where unconfined aquifers provide groundwater to support crop production on coarse soils. This is the first study in the Midwest United States to observe and quantify differences in regional climate associated with irrigated agricultural conversion from forests and rainfed agriculture. To this end, we established a 60 km transect consisting of 28 stations across varying land uses and monitored surface air temperature and relative humidity for 31 months in the Wisconsin Central Sands region. We used a novel approach to quantify irrigated land use in both space and time with a database containing monthly groundwater withdrawal estimates by parcel for the state of Wisconsin. Irrigated agriculture decreased maximum temperatures and increased minimum temperatures, thus shrinking the diurnal temperature range (DTR) by an average of 3 degrees C. Irrigated agriculture also decreased the vapor pressure deficit (VPD) by an average of 0.10 kPa. Irrigated agriculture significantly decreased evaporative demand for 25% and 66% of study days compared to rainfed agriculture and forest, respectively. Differences in VPD across the land-use gradient were highest (0.21 kPa) during the peak of the growing season, while differences in DTR were comparable year-round. Interannual variability in temperature had greater impacts on differences in DTR and VPD across the land-use gradient than interannual variability in precipitation. These regional climate changes must be considered together with increased greenhouse gas emissions, changes to groundwater quality, and surface water degradation when evaluating the costs and benefits of groundwater-sourced irrigation expansion in the Midwest United States and similar regions around the world.