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Excess nitrogen (N) impairs inland water quality and creates hypoxia in coastal ecosystems. Agriculture is the primary source of N; agricultural management and hydrology together control aquatic ecosystem N loading. Future N loading will be determined by how agriculture and hydrology intersect with climate change, yet the interactions between changing climate and water quality remain poorly understood. Here, we show that changing precipitation patterns, resulting from climate change, interact with agricultural land use to deteriorate water quality. We focus on the 2012–2013 Midwestern U.S. drought as a “natural experiment”. The transition from drought conditions in 2012 to a wet spring in 2013 was abrupt; the media dubbed this “weather whiplash”. We use recent (2010–2015) and historical data (1950–2015) to connect weather whiplash (drought-to-flood transitions) to increases in riverine N loads and concentrations. The drought likely created highly N-enriched soils; this excess N mobilized during heavy spring rains (2013), resulting in a 34% increase (10.5 vs. 7.8 mg N L−1) in the flow-weighted mean annual nitrate concentration compared to recent years. Furthermore, we show that climate change will likely intensify weather whiplash. Increased weather whiplash will, in part, increase the frequency of riverine N exceeding E.P.A. drinking water standards. Thus, our observations suggest increased climatic variation will amplify negative trends in water quality in a region already grappling with severe impairments.