The Grafs-Seneque/Riverstrahler model was implemented for the first time on the Loire River for the 2002–2014 period, to explore eutrophication after improvement of wastewater treatments. The model reproduced the interannual levels and seasonal trends of the major water quality variables. Although eutrophication has been impressively reduced in the drainage network, a eutrophication risk still exists at the coast, as shown by the N-ICEP indicator, pointing out an excess of nitrogen over silica and phosphorus. From maximum biomass exceeding 120 μgChla l−1 in the 1980's, we observed decreasing maximum values from 80 to 30 μgChla l−1 during the period studied. Several scenarios were explored. Regarding nutrient point sources, a low wastewater treatment scenario, similar to the situation in the 1980's, was elaborated, representing much greater pollution than the reference period (2002–2014). For diffuse sources, two agricultural scenarios were elaborated for reducing nitrogen, one with a strict application of the agricultural directives and another investigating the impact of radical structural changes in agriculture and the population's diet. Although reduced, a risk of eutrophication would remain, even with the most drastic scenario. In addition, a pristine scenario, with no human activity within the basin, was devised to assess water quality in a natural state. The impact of a change in hydrology on the Loire biogeochemical functioning was also explored according to the effect of climate change by the end of the 21st century. The EROS hydrological model was used to force Riverstrahler, considering the most pessimistic SRES A2 scenario run with the ARPEGE model. Nutrient fluxes all decreased due to a >50% reduction in the average annual discharge, overall reducing the risk of coastal eutrophication, but worsening the water quality status of the river network. The Riverstrahler model could be useful to help water managers contend with future threats in the Loire River, at the scale of its basin and at smaller nested scales.