 Despite decades of water protection programmes, ecological targets for European water bodies have not been met due to inadequate consideration of whole river network perspectives and interactions between stream orders, spatial patterns of pollutant sources, and eco-region dependent susceptibility. Using high-resolution data from Germany, we found that the ecological status of good or better was achieved in less than 8% of all river sections, with the highest proportions in low-order streams. Increasing agricultural land use fraction impaired ecological status across all stream orders, while relationships between urban wastewater river discharge fraction and ecological status were significant only in low-order streams. Concentrating integrative restoration efforts in low-order streams would maximise the potential to mitigate anthropogenic impacts. This article was authored by Olaf Butner, James W. Jowitz, and Dietrich Bortschart.