Water availability for human and ecosystem needs is a function of both water quantity and water quality, as described in the U.S. Geological Survey (USGS) Water Science Strategy (Evenson and others, 2013). Recently, a quantitative approach to prioritize candidate watersheds for monitoring investment was developed to understand changes in water availability and advance the objectives of new USGS programs (Van Metre and others, 2020). In this study design, the contiguous United States (CONUS) was divided into 18 regions (referred to here as “hydrologic regions” or “HRs”) with relatively homogeneous hydrologic drivers and processes to represent the wide diversity in conditions that exist across the CONUS. The gap analysis focused on prioritizing new capabilities beyond the current USGS science in discharge and constituent concentration trends to develop integrated capabilities for assessing and modeling of the water-quality drivers of aquatic ecosystem health. Water availability can be limited by various water-quality parameters such as temperature, salinity, excess nutrients, suspended sediment, geogenic constituents, and other contaminants of emerging concern (CECs) depending on water sources and human or ecosystem needs (Stanton and others, 2017). This data release contains more than 100 geospatial variables summarized for each watershed at the Hydrologic Unit level 4 (HUC4) that were used to prioritize watersheds targeted for USGS research. Additionally, the data release includes the polygon layers of the modified HUC4 watersheds and the hydrologic regions used for the analyses.