Dissolved oxygen (DO) sustains river ecosystems, but the effects of hydrological extremes remain poorly understood. While high river discharge (Q) enhances aeration, floods also deliver oxygen-consuming pollutants, making net impacts uncertain. Here, we analyze daily DO and its percent saturation (DO%sat), and Q in 1156 Chinese rivers over three years. We show that DO and DO%sat decrease with rising Q in 69.1% and 55.7% of rivers, respectively. Floods (Q > 95th percentile) cause abrupt declines in both DO (19.7%) and DO%sat (16.2%) in 80.1% and 69.4% of the rivers, respectively, with the sharpest declines in agricultural and urban areas. These abrupt deoxygenation events link to increased ammonium and land-use intensity, causing more frequent hypoxia in developed regions. Contrary to initial expectations, floods often reduce oxygen levels, with faster recovery in urbanized regions. As climate change intensifies flooding, such sudden deoxygenation shocks may degrade aquatic ecosystems particularly in human-altered landscapes.