Background Sharp increases in food production worldwide are attributable to agricultural intensification aided by heavy use of agrochemicals. This massive use of pesticides and fertilizers in combination with global climate change has led to collateral damage in freshwater systems, notably an increase in the frequency of harmful cyanobacterial blooms (HCBs). The precise mechanisms and magnitude of effects that pesticides exert on HCBs formation and proliferation have received little research attention and are poorly constrained. Results We found that azoxystrobin (AZ), a common strobilurin fungicide, can favor cyanobacterial growth through growth inhibition of eukaryotic competitors (Chlorophyta) and possibly by inhibiting cyanobacterial parasites (fungi) as well as pathogenic bacteria and viruses. Meta-transcriptomic analyses identified AZ-responsive genes and biochemical pathways in eukaryotic plankton and bacteria, potentially explaining the microbial effects of AZ. Conclusions Our study provides novel mechanistic insights into the intertwined effects of a fungicide and eutrophication on microbial planktonic communities and cyanobacterial blooms in a eutrophic freshwater ecosystem. This knowledge may prove useful in mitigating cyanobacteria blooms resulting from agricultural intensification.