The Red River (North Vietnam) is a typical example of a subtropical Asian river system undergoing high human pressure. During the last 50 years, major changes have occurred in its watershed, extending over an area of 156,450 km2 in Vietnam and China. We provide a detailed account of these changes, related to intensification of agriculture, deforestation, increase in population and urbanization, impoundment of reservoirs, etc. This information is used in a modeling approach of the nutrient transfers and transformations along the river system, in order to evaluate the changes in water quality of the Red River and its potential for coastal eutrophication. We conclude that the combination of increased nitrogen release from agriculture and retention of phosphorus in the reservoirs has considerably changed the balance of nutrients delivered at the outlet of the river, bringing the system close to a turning point in its nutrient biogeochemistry and its potential for coastal eutrophication. The upcoming impoundment of four new major dams in the watershed makes this conclusion particularly relevant.