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Formed at the confluence of marine and fresh waters, estuaries experience both the seaside pressures of rising sea levels and increasing storm severity, and watershed and precipitation changes that are shifting the quality and quantity of freshwater and sediments delivered from upstream sources. Boating, shoreline hardening, harvesting pressure, and other signatures of human activity are also increasing as populations swell in coastal regions. Given this shifting landscape of pressures, the factors most threatening to estuary health and stability are often uncertain. To identify the greatest contemporary threats to coastal wetlands and oyster reefs across the southeastern United States (Mississippi to North Carolina), we summarized recent population growth and land-cover change and surveyed estuarine management and science experts. From 1996 to 2019, human population growth in the region varied from a 17% decrease to a 171% increase (mean = +43%) with only 5 of the 72 SE US counties losing population, and nearly half growing by more than 40%. Individual counties experienced between 999 and 19,253 km2 of new development (mean: 5725 km2), with 1–5% (mean: 2.6%) of undeveloped lands undergoing development over this period across the region. Correspondingly, our survey of 169 coastal experts highlighted development, shoreline hardening, and upstream modifications to freshwater flow as the most important local threats facing coastal wetlands. Similarly, experts identified development, upstream modifications to freshwater flow, and overharvesting as the most important local threats to oyster reefs. With regards to global threats, experts categorized sea level rise as the most pressing to wetlands, and acidification and precipitation changes as the most pressing to oyster reefs. Survey respondents further identified that more research, driven by collaboration among scientists, engineers, industry professionals, and managers, is needed to assess how precipitation changes, shoreline hardening, and sea level rise are affecting coastal ecosystem stability and function. Due to the profound role of humans in shaping estuarine health, this work highlights that engaging property owners, recreators, and municipalities to implement strategies to improve estuarine health will be vital for sustaining coastal systems in the face of global change. [Display omitted] • Between 1996 and 2019, coastal counties in the southeastern US grew by −17%–171%. • Regionally, 2.6% of undeveloped lands were developed between 1996 and 2016. • Coastal experts cite development as greatest local threat to wetlands and oysters. • Experts cite sea level rise as greatest global threat to SE US wetlands. • Acidification and changing rainfall cited as key global threats to SE US oysters. [ABSTRACT FROM AUTHOR]