Global transition towards renewable energy production has increased the demand for new and more flexible hydropower operations. Before management and stakeholders can make informed choices on potential mitigations, it is essential to understand how the hydropower reservoir ecosystems respond to water level regulation (WLR) impacts that are likely modified by the reservoirs' abiotic and biotic characteristics. Yet, most reservoir studies have been case-specific, which hampers large-scale planning, evaluation and mitigation actions across various reservoir ecosystems. Here, we investigated how the effect of the magnitude, frequency and duration of WLR on fish populations varies along environmental gradients. We used biomass, density, size, condition and maturation of brown trout (Salmo trutta L.) in Norwegian hydropower reservoirs as a measure of ecosystem response, and tested for interacting effects of WLR and lake morphometry, climatic conditions and fish community structure. Our results showed that environmental drivers modified the responses of brown trout populations to different WLR patterns. Specifically, brown trout biomass and density increased with WLR magnitude particularly in large and complex-shaped reservoirs, but the positive relationships were only evident in reservoirs with no other fish species. Moreover, increasing WLR frequency was associated with increased brown trout density but decreased condition of individuals within the populations. WLR duration had no significant impacts on brown trout, and the mean weight and maturation length of brown trout showed no significant response to any WLR metrics. Our study demonstrates that local environmental characteristics and the biotic community strongly modify the hydropower-induced WLR impacts on reservoir fishes and ecosystems, and that there are no one-size-fits-all solutions to mitigate environmental impacts. This knowledge is vital for sustainable planning, management and mitigation of hydropower operations that need to meet the increasing worldwide demand for both renewable energy and ecosystem services delivered by freshwaters.