Humans have increased the discharge of pollution, altered water flow regime and modified the morphology of rivers. All these actions have resulted in multiple pressures on freshwater ecosystems, undermining their biodiversity and ecological functioning. The European Union has adopted an ambitious water policy to reduce pressures and achieve a good ecological status for all water bodies. However, assessing multiple pressures on aquatic ecosystems and understanding their combined impact on the ecological status is challenging, especially at the large scale, though crucial to the planning of effective policies. Here, for the first time, we quantify multiple human pressures and their relationship with the ecological status for all European rivers. We considered ecological data collected across Europe and pressures assessed by pan-European models, including pollution, hydrological and hydromorphological alterations. We estimated that in one third of EU's territory rivers are in good ecological status. We found that better ecological status is associated with the presence of natural areas in floodplains, while urbanisation and nutrient pollution are important predictors of ecological degradation. We explored scenarios of improvement of rivers ecological status for Europe. Our results strengthen the need to halt urban land take, curb nitrogen pollution and maintain and restore nature along rivers.