Inputs of fresh water and grazing both can control aquatic food webs, but little is known about the relative strengths of and interactions between these controls. We use long-term data on the food web of the freshwater Hudson River estuary to investigate the importance of, and interactions between, inputs of fresh water and grazing by the invasive zebra mussel (Dreissena polymorpha). Both freshwater inputs and zebra mussel grazing have strong, pervasive effects on the Hudson River food web. High flow tended to reduce population size in most parts of the food web. High grazing also reduced populations in the planktonic food web, but increased populations in the littoral food web, probably as a result of increases in water clarity. The influences of flow and zebra mussel grazing were roughly equal (i.e., within a factor of 2) for many variables over the period of our study. Zebra mussel grazing made phytoplankton less sensitive to freshwater inputs, but water clarity and the littoral food web more sensitive to freshwater inputs, showing that interactions between these two controlling factors can be strong and varied.