Responses of marine invertebrates to anthropogenic noise are insufficiently known, impeding our understanding of ecosystemic impacts of noise and the development of mitigation strategies. We show that the blue mussel, Mytilus edulis, is negatively affected by ship-noise playbacks across different levels of biological organization. We take a novel mechanistic multi-method approach testing and employing established ecotoxicological techniques (i.e. Comet Assay and oxidative stress tests) in combination with behavioral and physiological biomarkers. We evidence, for the first time in marine species, noise-induced changes in DNA integrity (six-fold higher DNA single strand-breaks in haemocytes and gill epithelial cells) and oxidative stress (68% increased TBARS in gill cells). We further identify physiological and behavioral changes (12% reduced oxygen consumption, 60% increase in valve gape, 84% reduced filtration rate) in noise-exposed mussels. By employing established ecotoxicological techniques we highlight impacts not only on the organismal level, but also on ecological performance. When investigating species that produce little visually obvious responses to anthropogenic noise, the above mentioned endpoints are key to revealing sublethal effects of noise and thus enable a better understanding of how this emerging, but often overlooked stressor, affects animals without complex behaviors. Our integrated approach to noise research can be used as a model for other invertebrate species and faunal groups, and inform the development of effective methods for assessing and monitoring noise impacts. Given the observed negative effects, noise should be considered a potential confounding factor in studies involving other stressors.