Drought occurs naturally due to variability in rainfall, but the frequency and severity of drought is increasing in many regions due to climate change (Trenberth et al., 2014). Hydrological drought has wide-ranging impacts on water quality, nutrients, carbon, and biota. This study investigated the effects of hydrological drought on historical streamflow patterns, water quality and macroinvertebrate metrics. We found that drought conditions affect water quality metrics, with changes in physicochemical, nutrient and carbon metrics. These changes were complex due to the regulation of the river and inputs from point and non-point sources. Further, we found that historical streamflows records showed broad declines over the southeastern U.S. with impacts being ecoregion specific. Additionally, these changes were spatially complex and likely from a range of causative factors. Finally, we found that streamflow declines were evident in individual basins and related to precipitation and drainage area. Given the uncertainty of climate change and the predicted increased frequency and severity of drought in the future, investigations into changes induced by drought are increasingly important.