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Changes in mixing regimes and CO2 availability may promote harmful cyanobacterial blooms in polymictic lakes and ponds globally, but the underlying mechanisms still remain unclear. We integrated results from a natural experiment comprising an average-wet year (2011) and one with heat waves (2012), a long-term meteorological dataset (1960–2010), historical phosphorus concentrations and corresponding sedimentary pigment records, to determine, on different temporal scales, the mechanistic controls of cyanobacterial blooms in a eutrophic polymictic lake. Intense warming in 2012 was associated with: 1) increased stability of the water column with buoyancy frequencies exceeding 40 cph at the surface, 2) high phytoplankton biomass in spring (up to 125 mg WW L-1), 3) reduced downward transport of heat and 4) persistently depleted epilimnetic CO2 concentrations. CO2 depletion was effectively maintained by intense uptake by phytoplankton (influx up to 30 mmol m-2 d-1) in combination with reduced carbon inputs from the watershed during dry periods. Under eutrophic conditions these effects triggered massive bloom of buoyant cyanobacteria (up to 300 mg WW L-1). Complementary evidence from polynomial regression modelling using long-term datasets revealed that warming is the most important predictor of cyanobacterial abundance during the second half of the last century explaining 78% of the observed positive trend, whereas phosphorus concentration explained only 10% thereof. Together the results from the interannual comparison and the multi-decadal record indicate that hotter and drier climates increase water column stratification and decrease CO2 availability in eutrophic polymictic lakes. This combination catalyzes blooms of buoyant cyanobacteria.