Long-term studies of macrophyte beds growing near streams in Conesus Lake, New York, have revealed a high biomass and continuing dominance of the invasive rooted species Eurasian watermilfoil (Myriophyllum spicatum). We tested whether agricultural best management practices (BMPs) designed to reduce tributary nutrient and soil loss from the watershed could reduce populations of Eurasian watermilfoil downstream in the lake littoral. Six macrophyte beds were monitored during a 3-year baseline period (2001–2003) prior to the implementation of BMPs and for a 4-year experimental period after a variety of agricultural BMPs were implemented in three sub-watersheds. For three macrophyte beds downstream from sub-watersheds managed as part of our project, quadrat biomass decreased by 30–50% and was statistically lower than Pre-BMP baseline values in 7 of 11 experimental sample years. Biomass loss primarily in the form of the dominant Eurasian watermilfoil ranged from 6.2 to 10 t wet weight for each bed. The declines in biomass coincided with significant annual and January—August decreases in the concentrations and fluxes of dissolved nutrients, total phosphorus, and total suspended solids in nearby streams. For three macrophyte beds downstream from watersheds in which landowners applied less extensive or no new agricultural management, biomass was statistically indistinguishable from Pre-BMP baseline values in all 12 experimental sample years. Milfoil remained the overwhelmingly dominant species at all sites during the entire study period. These results provide impetus for the use of watershed nutrient management to control the nuisance growth of Eurasian Watermilfoil on a local scale in the lake littoral.