Microcystis aeruginosa is known as the main contributor to cyanobacterial bloom, which is prevalent globally and degrades freshwater systems worldwide. The argument that the introduction of anthropogenic contaminants in fresh water stimulates cyanobacterial growth and microcystin production has attracted widespread attention. Bisphenol A (BPA), one of the most abundant endocrine-disrupting compounds, is often detected in various water bodies due to its notably high annual levels of production and use. Research on the combined effects of endocrine-disrupting compounds and environmental factors on cyanobacteria remains limited. To investigate the mechanism of interactions between contaminants and cyanobacteria at the cellular and proteomic levels, the growth rate, chlorophyll-a content, photosynthetic activities, microcystin-LR (MC-LR) production and release, reactive oxygen species (ROS) content, superoxide dismutase (SOD) activities, malondialdehyde (MDA) content, and proteome expression of M. aeruginosa under 1 μM BPA stress at a standard phosphorus level were investigated. The results showed that stress responses to BPA included increases in the growth rate, chlorophyll-a content, and Fv/Fm and rETRmax values under the low phosphorus condition. Responses involving ROS, SOD, and MDA indicated that phosphorus sufficiency and BPA caused oxidative stress in M. aeruginosa. Moreover, phosphorus sufficiency and BPA stimulated the production and release of MCs. Compared to levels in the non-BPA-treated group, exposure of M. aeruginosa to BPA caused 72 up-regulated proteins, which were primarily associated with photosynthesis, ribosome, fatty acid biosynthesis, glycolysis/glyconeogenesis, and carbon fixation in photosynthetic organisms. The 105 down-regulated proteins were related to quorum sensing, base excision repair, ABC transporters, longevity regulating and cell cycle-caulobacter, suggesting that the cytotoxicity of cyanobacterial cells induced by BPA was significantly increased. These findings provide insights into the molecular mechanism of the effects of BPA and phosphorus on M. aeruginosa, suggesting that coexisting pollutants may cause greater harm to and health risks in the environment.