It is broadly acknowledged that freshwater ecosystems are affected by multiple stressors, but the relative importance of individual stressors in impairing riverine communities remains unclear. We investigated the impacts of multiple stressors, incorporating in-stream water quality, riparian and catchment land use and stream morphology, on riverine benthic invertebrate communities, while considering the spatial scales of factors and the heterogeneity of riverscapes. We performed a stepwise regression procedure linking 21 abiotic and 20 community metrics using Generalized Linear Models on data from 1018 river sites spread across Germany. High impact stressors (e.g., nutrients and water temperature) were identified for various community metrics. Both the combination of relevant stressors and their explanatory value differed significantly across streams of different sizes and ecoregions. In large rivers, the riparian land use was less important in determining community structure compared to lower order streams. Thus, possible mitigating effects of revegetated riparian buffer strips are likely to be overwhelmed by the influence of catchment-wide land use. Our results indicated substantial variability in stressors for the range of metrics studied, providing insight into potential target parameters for effective ecosystem management. To achieve long lasting successes in managing, protecting and restoring running waters, it is of vital importance to recognize the heterogeneity of riverscapes and to consider large-scale influences.