Agricultural intensification in semiarid regions comes at a cost of relatively high water losses through evapotranspiration and can contribute to releases of nutrients and pesticides that affect downstream water quality. In addition, highly managed river basins may be particularly sensitive to future climate change. However, effects on retention-attenuation of nutrients are difficult to quantify due to the complexity and variability of relevant processes. We here use the example case of the large (covering 1.3% of the earth's land surface) and extensively irrigated Aral Sea Drainage Basin (ASDB) in Central Asia, together with 73 general circulation model (GCM) projection results and field-data driven nitrogen retention-attenuation modeling, to investigate to which extent projected future climate change (for years 2025, 2050 and 2100) can influence nitrogen loads and concentrations in the water systems of the basin. Results for the principal Amu Darya River of the ASDB suggest that riverine concentrations of nitrogen will decrease considerably throughout the coming century. This is due to projected climate-related decreases in runoff and river discharge, which increases internal nitrogen recirculation ratios, average transport distances and nitrogen retention-attenuation. However, in groundwater near the agricultural fields, there is in contrast a risk of considerable nitrogen accumulation. More generally, the sensitivity of nitrogen concentrations in the ADRB to climate-driven changes in runoff and discharge is likely to be shared with many highly managed basins in arid and semiarid regions of Central Asia, and the world.