ABSTRACT Little is known about the molecular and physiological function of co-occurring microbes within freshwater cyanobacterial harmful algal blooms (cHABs). To address this, community metatranscriptomes collected from the western basin of Lake Erie during August 2012 were examined. Using sequence data, we tested the hypothesis that the activity of the microbial community members is independent of community structure. Predicted metabolic and physiological functional profiles from spatially distinct metatranscriptomes were determined to be ≥90% similar between sites. Targeted analysis of Microcystis aeruginosa , the historical causative agent of cyanobacterial harmful algal blooms over the past ∼20 years, as well as analysis of Planktothrix agardhii and Anabaena cylindrica , revealed ongoing transcription of genes involved in microcystin toxin synthesis as well as the acquisition of both nitrogen and phosphorus, nutrients often implicated as independent bottom-up drivers of eutrophication in aquatic systems. Transcription of genes involved in carbon dioxide (CO ₂ ) concentration and metabolism also provided support for the alternate hypothesis that high-pH conditions and dense algal biomass result in CO ₂ -limiting conditions that further favor cyanobacterial dominance. Additionally, the presence of Microcystis -specific cyanophage sequences provided preliminary evidence of possible top-down virus-mediated control of cHAB populations. Overall, these data provide insight into the complex series of constraints associated with Microcystis blooms that dominate the western basin of Lake Erie during summer months, demonstrating that multiple environmental factors work to shape the microbial community.