In this paper, we frame the problem of urban water sustainability in megacities as a social-ecological system (SES) to examine the underlying coupling of social and ecological factors and processes. Based on our empirical research of two major megacities of the global south, São Paulo and Delhi, we have developed an urban water SES module within the broader SES framework proposed by Ostrom. The module’s multilevel nested structure consists of the following four subsystems: water resource and infrastructure, settlements, governance, and actors. A distinct advantage of our module is that it enables us to capture the plurality of settlements patterns (from formal to informal settlements), actor networks, and governance patterns found in cities of the global south and how these uniquely shape and are shaped by the process of rapid urbanization. We use this module as: (a) an analytical tool to identify the different variables and processes within each subsystem, which through their interactions, have influenced the trajectory of water systems in these cities; (b) a diagnostic tool in a comparative setting to examine why desired goals in terms of service delivery and/or governance were achieved (or not); and (c) a prescriptive tool to identify cross-learnings and practical lessons.