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Climate change elevates the threat of compound heat and drought events, with their ecological and socioeconomic impacts exacerbated by human ecosystem alterations such as eutrophication, salinization, and river engineering. Here, we study how multiple stressors produced an environmental disaster in a large European river, the Oder River, where a toxic bloom of the brackish-water planktonic haptophyte Prymnesium parvum (the "golden algae") killed approximately 1000 metric tons of fish and most mussels and snails. We uncovered the complexity of this event using hydroclimatic data, remote sensing, cell counts, hydrochemical and toxin analyses, and genetics. After incubation in impounded upstream channels with drastically elevated concentrations of salts and nutrients, only a critical combination of chronic salt and nutrient pollution, acute high water temperatures, and low river discharge during a heatwave enabled the riverine mass proliferation of B-type P. parvum along a 500 km river section. The dramatic losses of large filter feeders and the spreading of vegetative cells and resting stages make the system more susceptible to new harmful algal blooms. Our findings show that global warming, water use intensification, and chronic ecosystem pollution could increase likelihood and severity of such compound ecoclimatic events, necessitating consideration in future impact models., (© 2024. The Author(s).)