Cyanobacterial blooms pose one of the most severe ecological challenges in aquatic systems. However, the mechanism through which bacterial dissolved organic matter influences the formation of algal blooms remains unclear. In this study, extracellular organic matter (EOM) was extracted from Flavobacterium sp., a common bacterial group in bloom, and the impacts of this EOM on the growth, physiology, photosynthesis, and transcriptome of Anabaena sp. were investigated. The results indicated that flavobacterium-derived EOM (F-EOM) inhibited Anabaena sp. growth, physiological activity, and photosynthesis, with greater inhibition at higher concentrations. Meanwhile, transcriptome analysis showed that 803 genes in Anabaena sp. were differentially expressed after being exposed to 10 mg/L F-EOM, with simultaneously the majority being down-regulated. The down-regulation of genes in photochemical reactions, the synthesis of photosynthetic pigment, and light-trapping antenna protein inhibited photosynthesis. While ATP synthesis was reduced due to the genes related to oxidative phosphorylation and the tricarboxylic acid cycle was downregulated. Moreover, the down-regulated genes in amino acid synthesis affected the synthesis of proteins and metabolic regulatory factors. This may be the main reason why F-EOM could hinder the growth and metabolism of Anabaena sp. These results provide scientific insights into the formation and control of cyanobacteria blooms.