As the Seine basin is the most urbanized and industrialized French basin, with intensive crop areas, the impact of floods and low flow is very important. The aim of this study is to improve the understanding of the hydrological functioning of the Seine basin and to estimate the influence of the large aquifers that cover a great part of the domain, as well as the impact of the urbanized areas. The simulation is based on the SAFRAN-ISBA-MODCOU (SIM) coupled system, which includes the Analysis System for Providing Atmospheric Information Relevant to Snow (SAFRAN) analysis of the atmospheric forcing, two surface schemes that take into account the urban areas (Town Energy Budget (TEB)) and the natural areas (Interactions Soil-Biosphere-Atmosphere (ISBA)), and the distributed hydrological model Coupled Model (MODCOU). A 17-year simulation was performed and validated against the observations of about 100 river gauges and 130 piezometric stations. The simulated streamflows are comparable with the observations, especially for large river stations of the Seine and its main tributaries. The spatial and temporal variations of the aquifer levels simulated by MODCOU are also comparable to the observed piezometric data, although the local comparison can present differences. The impact of urban areas on the streamflows appears to be important at the local scale but not very marked at the basin scale, but their impact on the energy budget is strong. Moreover, it is shown that the aquifers play a very important role. The underground contribution to the discharge reaches more than 80% of the Seine river flow in summertime and ~40% in winter. Even during the wintertime floods, the aquifers play a crucial role, since the larger part of the drainage is stored in the water tables, which significantly reduces the intensity of the floods and, thus, of their consequences. It is finally shown that the ability of SIM to reproduce the evolution of the aquifers and the partition between surface runoff and drainage leads to a good simulation of the main floods of the Seine.