Water security is tightly connected with the food security, ecological health, and economic prosperity of a region. In this study, a comprehensive water security assessment based on water footprint concepts from 1995 to 2015 was performed for the counties located in the Contiguous States of the Unites States. The availability of blue water (e.g., surface water) is comparatively less in the western river basins, and most of the rainfed agricultural lands in the eastern United States were characterized by the lower levels of green water (e.g., root zone soil moisture) storage. This integrated assessment of the water security indicators can directly map the critical regions and reveal the dependence between human water consumption, crop water requirements and environmental flow. This analysis can be further extended to incorporate climate change and extreme drought events to inform specific locations (e.g., counties and watersheds) at which problems of water conflict are more likely to occur. Plain Language Summary The spatial and temporal changes in climate variables (e.g., precipitation and temperature) control the water supply within a river basin. Concurrently, variability in sectorial water demands is determined by agricultural and human usage within a river basin. Therefore, it is important to integrate supply and demand components to investigate water security within a river basin. This study investigates the spatiotemporal variability of water security indicators such as blue water scarcity, green water scarcity, and Falkenmark Indicators across the major river basins of the continental United States. We provide a first-ever assessment of water security based on climate and demand-driven water availability based on the selected sectors for the 18 major river basins of the CONUS (Contiguous States of the Unites States). We believe that our findings will provide insight into water supply and demand and related water security components in the CONUS. The results of this analysis will be useful in developing regional water management programs as well as in identifying key vulnerable river basins in the CONUS.