In 2018, the U.S. National Oceanographic and Atmospheric Administration (NOAA) and the U.S. Navy initiated a multi-year effort to monitor underwater sound using a standardized methodology within U.S. National Marine Sanctuaries (NMS). The agencies with numerous collaborators set out to study sound and its sources within seven NMS and one Marine National Monument, which includes waters off the east coast, west coast, and Pacific region of the U.S. The project was designed to provide information important for contextualizing contributions of sound by specific sources and their impacts on the soundscape, marine taxa, and habitats. Within the east coast region, sound is being recorded continuously at Stellwagen Bank, Gray’s Reef, and Florida Keys NMS, and data collected in 2018-2019 were analyzed to produce comparable soundscape statistics and detections of regionally important sound producers, which include invertebrates, fishes, marine mammals, and vessels. Differences in ambient sound were observed among sites with major contributors of snapping shrimp, fish, whales, and vessels to the soundscape at varying spatio-temporal scales. Results of the study highlight the potential of acoustic monitoring to assess ecosystem health, populations and behaviors of protected (e.g. whales) and commercially important species (e.g. Atlantic cod, grouper-snapper complex), and usage by stakeholders (e.g. vessels) within protected areas. Data are publicly available through NOAA’s National Center for Environmental Information (NCEI), and a web portal is under development to provide further public access and exploration of findings. This effort has and will continue to provide information about soundscapes and marine resources at national and regional scales and establishes a precedence for expansion to other priority areas for management.