Historical changes in land use on coastal watersheds have increased rates of land-derived nitrogen loading to estuaries and altered their biogeochemistry and food webs. We used information on human populations and land uses within the watershed of Waquoit Bay, Cape Cod, Massachusetts, U.S.A., to model how nitrogen loads derived from atmospheric deposition, fertilizer use, and wastewater disposal have changed since the 1930s. Nitrogen loading into Waquoit Bay more than doubled between 1938 and 1990. The predominant source of nitrogen added to the bay changed from atmospheric deposition to wastewater disposal during the 1980s, reflecting the increasing urbanization of Cape Cod. Larger nitrogen loads increased nitrogen concentrations in the water, altering the assemblage of primary producers and resulting in eutrophication of the estuary. Biomass of phytoplankton and macroalgae increased, and areal cover of eelgrass (Zostera marina) decreased, with increasing nitrogen load. An increase in nitrogen load from 15 to 30 kg N·ha1·year1 virtually eliminated eelgrass meadows. Land-use changes prompted by urban sprawl can therefore be linked to marked changes in water quality and eutrophication of receiving waters.