The Indus River Basin faces severe water quality degradation because of nutrient enrichment from human activities. Excessive nutrients in tributaries are transported to the river mouth, causing coastal eutrophication. This situation may worsen in the future because of population growth, economic development, and climate change. This study aims at a better understanding of the magnitude and sources of current (2010) and future (2050) river export of total dissolved nitrogen (TDN) by the Indus River at the sub-basin scale. To do this, we implemented the MARINA 1.0 model (Model to Assess River Inputs of Nutrients to seAs). The model inputs for human activities (e.g., agriculture, land use) were mainly from the GLOBIOM (Global Biosphere Management Model) and EPIC (Environmental Policy Integrated Model) models. Model inputs for hydrology were from the Community WATer Model (CWATM). For 2050, three scenarios combining Shared Socio-economic Pathways (SSPs 1, 2 and 3) and Representative Concentration Pathways (RCPs 2.6 and 6.0) were selected. A novelty of this study is the sub-basin analysis of future N export by the Indus River for SSPs and RCPs. Result shows that river export of TDN by the Indus River will increase by a factor of 1.6–2 between 2010 and 2050 under the three scenarios. >90% of the dissolved N exported by the Indus River is from midstream sub-basins. Human waste is expected to be the major source, and contributes by 66–70% to river export of TDN in 2050 depending on the scenarios. Another important source is agriculture, which contributes by 21–29% to dissolved inorganic N export in 2050. Thus a combined reduction in both diffuse and point sources in the midstream sub-basins can be effective to reduce coastal water pollution by nutrients at the river mouth of Indus.