Many water resources are threatened with nutrient pollution worldwide. This holds for rivers exporting increasing amounts of nutrients from the intensification of food production systems and further urbanization. This riverine nutrient transport causes coastal eutrophication. This study aims to identify cost-effective management options to simultaneously reach environmental targets for river export of nitrogen and phosphorus by the Yangtze River (China) in 2050. A newly developed modelling approach is used that integrates the Model to Assess River Inputs of Nutrients to seAs (MARINA) with a cost-optimization procedure, and accounts for socio-economic developments, land use and climate changes in a spatially explicit way. The environmental targets for river export of nutrients aim to reduce the gap between baseline and desirable nutrient export. Our baseline is based on MARINA projections for future river export of nutrients, while the desirable nutrient export reflects a low eutrophication potential. Results show the possibilities to close the gap in river export of both nutrients by 80–90% at a cost of 1–3 billion $ per year in 2050. Recycling of animal waste on cropland is an important cost-effective option; reducing synthetic fertilizer inputs provides an opportunity to compensate for the additional costs of the recycling and treatment of manure and wastewater. Our study provides new insights on the combination of cost-effective management options for sub-basins of the Yangtze. This can support the design of cost-effective and sub-basin specific management options for reducing future water pollution.