The Rio Grande River Basin spanning over Colorado, New Mexico, Texas, and Mexico presents a big challenge in terms of efficient water management. Water is allocated by a wide range of relatively autonomous water authorities in different regions of the river basin. Moreover, growing population in adjacent cities and the resulting increase in water demand as well as simultaneously shrinking water resources (due to climatic conditions and consumption patterns) create a need for evaluating water use as a sustainability problem described with economic, environmental, and social indicators. The goal of this study is to evaluate: 1) regional and temporal changes in municipal and total water use across the Rio Grande river counties adjacent to the river, and 2) relationships between socio-economic and environmental sub-indicators and water use in three case study counties: Rio Grande county in Colorado, Bernalillo county in New Mexico, and El Paso county in Texas. Key findings in this research show that in the majority of analyzed counties there is a strong relationship between water use and per capita personal income as well as public supply population (social sub-indicators). Only in around half of the counties with water rate data was a strong relationship between water use and water rates was found (economic sub-indicators). Moreover, there were few to no relationships detected between water use and temperature, precipitation or stream flow rate (environmental sub-indicators). This shows that social sub-indicators had the strongest relationship patterns where the environmental sub-indicators had the weakest relationship patterns. Water and sustainability managers can use the analysis of correlation significance for their counties as a basis for further investigation to better understand and design sustainable water management approaches.