The Gulf of Lions (GoL) is among the most productive areas of the Mediterranean Sea, with the Rhône River contributing with as much as 90% of the liquid and solid materials (including anthropogenic chemicals) reaching the area. In this paper, we assessed whether classical descriptive ecology and MaxEnt predictive species distribution modelling were able to provide complementary information when analysing the long-distance influence of the river discharges on the GoL benthic ecosystem. Samples were collected in August 2014 from 12 stations covering the sedimentary plain of the deep submarine delta, from the Gulf of Fos to Gruissan. Sediments were mostly muddy with a high organic carbon and low P and N contents first decreasing and then increasing from east to west. The same pattern occurred for chlorophyll-a, particulate organic carbon and sea surface temperature, and was overall correlated with metal and pollutant contents derived from agricultural, port, urban and industrial sources driven by Rhône outputs. We observed a typical deltaic succession in the benthos, showing a relatively low diversity and including polychaetes (Sternaspis scutata) and holothurians (Oestergrenia digitata) known to be indicators of high sedimentation rates. Overall, benthos showed an inversed pattern regarding environmental variables, an evident consequence of the Rhône River influence. The suitability of some species was either positively or negatively correlated with some of the environmental variables, producing species-specific predicted distribution patterns, with the highest amount of information allowing to predict distributions being mainly provided by organic pollutants. Even with a limited number of available samples, our integrated approach reveals to be a very robust tool to highlight hidden patterns and contributes to improve our knowledge on how river-mediated anthropogenic discharges may influence biodiversity distribution and functional patterns in marine benthic ecosystems.