Climate change and other anthropogenic stressors are converging on coastal ecosystems worldwide. Understanding how these stressors interact to affect ecosystem structure and function has immediate implications for coastal planning, however few studies quantify stressor interactions. We examined past and potential future interactions between two leading stressors on New England salt marshes: sea-level rise and marsh crab (Sesarma reticulatum) grazing driven low marsh die-off. Geospatial analyses reveal that crab-driven die-off has led to an order of magnitude more marsh loss than sea-level rise between 2005 and 2013. However, field transplant experimental results suggest that sea-level rise will facilitate crab expansion into higher elevation marsh platforms by inundating and gradually softening now-tough high marsh peat, exposing large areas to crab-driven die-off. Taking interactive effects of marsh softening and concomitant overgrazing into account, we estimate that even modest levels of sea-level rise will lead to levels of salt marsh habitat loss that are 3x greater than the additive effects of sea-level rise and crab-driven die-off would predict. These findings highlight the importance of multiple stressor studies in enhancing mechanistic understanding of ecosystem vulnerabilities to future stress scenarios and encourage managers to focus on ameliorating local stressors to break detrimental synergisms, reduce future ecosystem loss, and enhance ecosystem resilience to global change.