Interactions among global change stressors and their effects at large scales are often proposed but seldom evaluated, in part due to lack of comprehensive, sufficiently long-term, and spatially-extensive datasets. Seagrasses, which provide nursery habitat, improve water quality, and constitute a globally-important carbon sink, are among the most vulnerable habitats on the planet. Here, we unite 31-years of high-resolution aerial monitoring and water quality data to elucidate the patterns and drivers of eelgrass (Zostera marina) abundance in Chesapeake Bay, USA, one of the largest and most valuable estuaries in the world, with an unparalleled history of regulatory efforts. We show that eelgrass cover has declined 29% in total since 1991, with wide-ranging and severe ecological and economic consequences. We go on to identify an interaction between decreasing water clarity and warming temperatures as the primary driver of this trend. Declining clarity has gradually reduced eelgrass over the past two decades, primarily in deeper beds where light is already limiting. In shallow beds, however, reduced visibility exacerbates the physiological stress of acute warming, leading to recent instances of decline approaching 80%. While degraded water quality has long been known to influence underwater grasses worldwide, we demonstrate a clear and rapidly emerging interaction with climate change. We highlight the urgent need to integrate a broader perspective into local water quality management, in the Chesapeake Bay and in the many other coastal systems facing similar stressors.