Dreissenid mussels (quagga and zebra mussels) are powerful ecosystem engineers in the Laurentian Great Lakes, causing short- and long-term changes to phytoplankton including eukaryotic algae and cyanobacteria. In western Lake Erie, invasive dreissenid mussels have been implicated in promoting harmful algal blooms (HABs) in part by selectively feeding on eukaryotic phytoplankton such as green algae and diatoms while rejecting cyanobacteria such as Microcystis aeruginosa. However, it is unknown whether dreissenid mussels will engage in prey switching and feed on M. aeruginosa as the preferred food particles are depleted. Our laboratory experiments evaluated the response of quagga mussels and M. aeruginosa strains collected from the same ecosystem to gain a better understanding of context-dependent interactions between two ecological stressors. We determined feeding rates of quagga mussels on a mixture of the unicellular green algae Chlamydomonas oblonga and seven unique strains of Microcystis aeruginosa isolated from Lake Erie. Quagga mussels depleted C. oblonga but did not engage in prey switching and did not feed on M. aeruginosa. The presence of microcystins associated with some strains reduced feeding on C. oblonga. As anthropogenic disturbances in freshwater systems rise, it is imperative to understand how multiple stressors regulate ecosystem dynamics.