Selective grazing by zebra mussels has altered phytoplankton communities in many North American lakes, but the specific changes are not the same in each ecosystem. Because of this variation in response, we investigated the impacts of zebra mussels on the plankton community of Lake Champlain with two objectives: first to determine whether zebra mussels increased the dominance of potentially toxic cyanobacteria in the phytoplankton, and second to explore the impact of zebra mussels on protozoans, rotifers, copepod nauplii, and other microzooplankton in the lower food web. Experiments were conducted in 200-L mesocosms filled with Lake Champlain water filtered through a 150-μm sieve to remove macrozooplankton. Zebra mussels were added to half of the mesocosms while the others were maintained as controls. Over a 96-hour experimental period, we tracked nitrogen and phosphorus concentration, chlorophyll α, microcystin concentration, and both phytoplankton and microzooplankton composition and abundance. We found an increase in SRP and total nitrogen concentration and a decrease in the ratio of TN:TP in the zebra mussel treatments over time. Microcystin was undetectable throughout the experiment using the ELISA assay. Phytoplankton biovolume, including cyanobacteria biovolume, declined significantly in the zebra mussel treatments, as did rotifer, protozoan and nauplii abundance. By both direct (consumption) and indirect (altered nutrient availabilities and increased competition) means, zebra mussels clearly seem capable of strongly influencing the lower planktonic foodweb in the many shallow water habitats of Lake Champlain.