Groundwater-influenced ecosystems (GIEs) are increasingly vulnerable due to groundwater extraction, land-use practices, and climate change. These ecosystems receive groundwater inflow as a portion of their baseflow or water budget, which can maintain water levels, water temperature, and chemistry necessary to sustain the biodiversity that they support. In some systems (e.g., springs, seeps, fens), this connection with groundwater is central to the system’s integrity and persistence. Groundwater management decisions for human use often do not consider the ecological effects of those actions on GIEs. This disparity can be attributed, in part, to a lack of information regarding the physical relationships these systems have with the surrounding landscape and climate, which may influence the environmental conditions and associated biodiversity. We estimate the vulnerability of areas predicted to be highly suitable for the presence of GIEs based on watershed (U.S. Geological Survey Hydrologic Unit Code 12 watersheds: 24–100 km2) and pixel (30 m × 30 m pixels) resolution in the Atlantic Highlands and Mixed Wood Plains EPA Level II Ecoregions in the northeastern United States. We represent vulnerability with variables describing adaptive capacity (topographic wetness index, hydric soil, physiographic diversity), exposure (climatic niche), and sensitivity (aquatic barriers, proportion urbanized or agriculture). Vulnerability scores indicate that ~26% of GIEs were within 30 m of areas with moderate vulnerability. Within these GIEs, climate exposure is an important contributor to vulnerability of 40% of the areas, followed by land use (19%, agriculture or urbanized). There are few areas predicted to be suitable for GIEs that are also predicted to be highly vulnerable, and of those, climate exposure is the most important contributor to their vulnerability. Persistence of GIEs in the northeastern United States may be challenged as changes in the amount and timing of precipitation and increasing air temperatures attributed to climate change affect the groundwater that sustains these systems.