Land forcing (water discharge and nutrient loads) is reported as one of the major sources of uncertainty limiting the capacity of marine biogeochemical models. Runoff from rivers and coastal plains delivers significant amounts of nutrients to the Mediterranean Sea from agricultural activities and urban wastewater. Several recent studies show that variations in river inputs may play a significant role in marine biogeochemical cycles and the planktonic food web throughout the entire basin. The aim of this study is to estimate the water dischargeas as well as nitrate (NO3) and phosphate (PO4) release into the Mediterranean Sea from basin-wide agriculture and inhabited areas through the implementation of the biogeochemical land-sea nutrient transfer processes within the agro-ecosystem model Lund Potsdam Jena managed Land for the Mediterranean (LPJmL-Med). The representation of the nutrient transfer from land to sea has been introduced into LPJmL-Med by considering the following processes: mineralization, denitrification, adsorption, remineralization, nitrification, and phytoplankton dynamics. A compilation of a new input data set of fertilizer, manure and wastewater nutrient content [1961–2005] has been added to the LPJmL-Med forcing data set. The first basin-wide LPJmL simulation at 1/12° indicates that the model succeeds in simulating the interannual variability of water discharge for the main rivers in the Mediterranean Sea, especially the Po, Rhone and Ebro Rivers. A very high correlation (R-square values higher than 0.94) is found for these three rivers. Results also show a good consistency between the simulated nutrients concentration (NO3 and PO4) and available in-situ data. River outflows of NO3 and PO4 exhibit opposite trends in the Mediterranean Sea. NO3 showed a more or less continuous increase from the beginning of the 1960s until the present in all three rivers. PO4 trends are more heterogeneous. There is a strong increase in PO4 between 1960 and 1980, followed by a decrease in mean annual fluxes from the second half of the 1980s as a consequence of the banning of phosphates in detergents, and the construction of wastewater treatment plants in the different countries. Results show that wastewater strongly contributes to the river phosphate fluxes, while both agriculture and wastewater control the nitrogen (mainly as NO3) fluxes from rivers to the Mediterranean Sea.