Since the term was coined in the Brundtland report in 1987, the issue of sustainable development has been challenged in terms of quantification. Different policy options may lend themselves more or less to the underlying principles of sustainability, but no analytical tools are available for a more in-depth assessment of the degree of sustainability. Overall, there are two major schools of thought employing the sustainability concept in managerial decisions: those of measuring and those of monitoring. Measurement of relative sustainability is the key issue in bridging the gap between theory and practice of sustainability of water resources systems. The objective of this study is to develop a practical tool for quantifying and assessing the degree of relative sustainability of water quality systems based on risk-based indicators, including reliability, resilience, and vulnerability. Current work on the Karoun River, the largest river in Iran, has included the development of an integrated model consisting of two main parts: a water quality simulation subroutine to evaluate Dissolved Oxygen Biological Oxygen Demand (DO-BOD) response, and an estimation of risk-based indicators subroutine via the First Order Reliability Method (FORM) and Monte Carlo Simulation (MCS). We also developed a simple waste load allocation model via Least Cost and Uniform Treatment approaches in order to consider the optimal point of pollutants control costs given a desired reliability value which addresses DO in two different targets. The Risk-based approach developed herein, particularly via the FORM technique, appears to be an appropriately efficient tool for estimating the relative sustainability. Moreover, our results in the Karoun system indicate that significant changes in sustainability values are possible through dedicating money for treatment and strict pollution controls while simultaneously requiring a technical advance along change in current attitudes for environment protection.