Vulnerability assessments combine quantitative and qualitative evaluations of the exposure, sensitivity, and adaptive capacity of species or natural communities to current and future threats. When combined with the economic, ecological or evolutionary value of the species, vulnerability assessments quantify the relative risk to regional species and natural communities and can enable informed prioritization of conservation efforts. Vulnerability assessments are common practice in conservation biology, including the potential impacts of future climate scenarios. However, geographic variation in scenarios and vulnerabilities is rarely quantified. This gap is particularly limiting for informing ecosystem management given that conservation practices typically vary by sociopolitical boundaries rather than by ecological boundaries. To support prioritization of conservation actions across a range of spatial scales, we conducted the Gulf Coast Vulnerability Assessment (GCVA) for four natural communities and eleven focal species around the Gulf of Mexico based on current and future threats from climate change and land-use practices out to 2060. We used the Standardized Index of Vulnerability and Value (SIVVA) tool to assess both natural community and species vulnerabilities. We observed greater variation across ecologically delineated subregions within the Gulf Coast of the U.S. than across climate scenarios. This novel finding suggests that future vulnerability assessments incorporate regional variation and that conservation prioritization may vary across ecological subregions. Across subregions and climate scenarios the most prominent threats were legacy effects, primarily from habitat loss and degradation, that compromised the adaptive capacity of species and natural communities. The second most important threats were future threats from sea-level rise. Our results suggest that the substantial threats species and natural communities face from climate change and sea-level rise would be within their adaptive capacity were it not for historic habitat loss, fragmentation, and degradation.