Water resources are fundamental for the social and economic development of a country and sustainability is the best approach to treat water-related problems. Therefore, sustainability studies of water resources are deemed urgent. Sustainability analysis methods should enable space-temporal monitoring, decision-making, and development of policies necessary for water governance. Furthermore, sustainability analysis methods should also integrate environment and socioeconomic variables into a single system. In this context, this study aimed to assess the water sustainability conditions of the River Grande Basin (BHRG), Brazil, before the implementation of the Integrated Water Resources Plan (IWRP), using the Barometer of Sustainability tool (BS). The River Grande basin was in an “almost unsustainable” condition and under high environmental stress. A significant imbalance between environmental and human well-being in the system was also observed. To achieve an acceptable sustainability condition, it is thus necessary to improve the environmental quality of the area. Among the priority thematic area, native vegetation recovery was the most urgent. Overall, the sustainability study based on the BS not only facilitates comprehension regarding environment and human interrelationships, but also provide references for policy formulations and water management.