Hurricanes that cause damage to lives and property are often accompanied by poor water quality that threatens the health of human communities and aquatic species. North Carolina has experienced 3 devastating 500-yr storms within 2 years; wastewater treatment plants and sanitary sewer overows occurred up to 300 km inland, as well as coal ash spills, breaches of confined animal feeding operation (CAFO) waste lagoons, and numerous fish kills. Many in-situ sensors went offline and hazardous conditions precluded field sampling during and after these events. Publicly available satellite data enables delineation of flooding over broad areas, which can aid in quantifying the extent of flood exposure and potential water quality impacts. We mapped flooding across the North Carolina Piedmont and Coastal Plain due to Hurricane Matthew (2016) and Hurricane Florence (2018) with Sentinel-1 synthetic aperture radar. We assessed how impacts were distributed across indicators of social vulnerability at the census tract level and freshwater ecological vulnerability at a watershed scale using quantile regression. Finally, we identied flood-prone infrastructure relevant to water supply and treatment, and mapped locations where nature-based solutions could be implemented to store floodwaters and process contaminants. Flooding mapped with >91% accuracy extended beyond the 500-year floodplain—furthermore, the legal floodplain systematically underestimated impacts to more vulnerable human populations and surface waters. Repeated flooding affected both point and non-point sources of nutrients, including 188 wastewater treatment plants representing >46% of treatment capacity and 77 swine CAFOs that generate ~ 478,926,961 tons of manure per year. Conservation of ~4,600 ha of currently unprotected forest and wetland, and restoration or changes in land management on ~3,100 ha represent key opportunities to protect human and natural communities under future storms. Our results suggest that current flood hazard maps are inadequate for resilience planning. Changes to design standards, land-use planning policies, and operation of infrastructure that conveys and treats water are warranted to improve floodplain resilience.