We quantified the vertical and horizontal variation of chlorophyll a (Chl-a) to test how benthic filter feeders (dreissenid mussels), rooted macrophytes, and hydrodynamics influence phytoplankton distributions in a large lake (Lake Simcoe, Canada). Water column Chl-a did not differ significantly among sites of different depth, distance offshore, or rooted macrophyte biomass, but among the nearshore sites (7.5–10 m deep) it was higher where mussel biomass was greater. This counterintuitive result may be explained by wind-driven horizontal circulation during our specific study periods together with the patchy distribution of the mussels in the lake. Information on mixing depths, vertical eddy diffusivity, and mussel biomass was used to predict when and where the grazing pressure of mussels would likely deplete near-bottom phytoplankton. Chl-a depletion was frequently predicted at sites with moderate or high mussel biomass and sufficient thermal stratification to impede vertical mixing but never at sites without thermal stratification. Observations were consistent with predictions in most cases. The results suggested that mussels at depths of 7.5–15 m (a depth range of generally high mussel biomass in the lake) may frequently suffer food limitation due to near-bottom depletion during the early and middle stratified season. A deep Chl-a maximum was documented and may be important for mussel nutrition at such times.