Human land uses and population growth represent major global threats to biodiversity and ecosystem services. Understanding how biological communities respond to multiple drivers of human-induced environmental change is fundamental for conserving ecosystems and remediating degraded habitats. Here, we used a replicated ‘real-world experiment’ to study the responses of invertebrate communities to wastewater perturbations across a land-use intensity gradient in 12 Swiss streams. We used different taxonomy and trait-based community descriptors to establish the most sensitive indicators detecting impacts and to help elucidate potential causal mechanisms of change. First, we predicted that streams in catchments adversely impacted by human land-uses would be less impaired by wastewater inputs because their invertebrate communities should be dominated by pollution-tolerant taxa (‘environmental context’). Second, we predicted that the negative effects of wastewater on stream invertebrate communities should be larger in streams that receive proportionally more wastewater (‘magnitude of disturbance’). In support of the ‘environmental context’ hypothesis, we found that change in the Saprobic Index (a trait-based indicator of tolerance to organic pollution) was associated with upstream community composition; communities in catchments with intensive agricultural land uses (e.g., arable cropping and pasture) were generally more resistant to eutrophication associated with wastewater inputs. We also found support for the ‘magnitude of disturbance’ hypothesis. The SPEAR Index (a trait-based indicator of sensitivity to pesticides) was more sensitive to the relative input of effluent, suggesting that toxic influences of wastewater scale with dilution. Whilst freshwater pollution continues to be a major environmental problem, our findings highlight that the same anthropogenic pressure (i.e., inputs of wastewater) may induce different ecological responses depending on the environmental context and community metrics used. Thus, remediation strategies aiming to improve stream ecological status (e.g., rehabilitating degraded reaches) need to consider upstream anthropogenic influences and the most appropriate indicators of restoration success.