Zebra mussels (ZM), Dreissena polymorpha (Pallas, 1771), are one of the most aggressive invasive species. ZM have a strong bidirectional impact on phytoplankton because of their high nutrient excretion rates and high grazing pressure. Furthermore, the interactions between excretion and selective grazing are related to the trophic status of a waterbody and could cause unpredictable changes in phytoplankton. We performed three types of experiments: (i) bottom-up where we measured ZM excretion rates; (ii) top-down where we analyzed the effects of ZM on phytoplankton taxonomic structure via grazing in different trophic conditions; (iii) mesocosm experiment where we estimated the combined top-down and bottom-up effects of ZM on phytoplankton assemblages under different trophic conditions. Our first experiment confirmed high excretion rates of dissolved nutrients (PO43− and NH4+) and dissolved organic carbon (DOC) by ZM. The other experiments revealed selective grazing by ZM, where diatoms were mostly selectively rejected, while green algae were preferred. In the top-down experiment, ZM decreased the total biomass of phytoplankton, while in mesocosm experiments where top-down and bottom-up controls acted simultaneously, we observed increased phytoplankton biomass mainly through increases in filamentous green algae. Our experiments show that ZM can influence phytoplankton through a combination of bottom-up and top-down effects that vary with trophic state.