In many countries of the Global South, aquatic ecosystems such as streams, rivers, lakes, and wetlands are severely impacted by several simultaneous environmental stressors, associated with accelerated urban development, and extreme climate. However, this problem receives little attention. Applying a DPSIR approach (Drivers, Pressures, State, Impacts, Responses), we analyzed the environmental impacts and their effects on urban hydrosystems (including stagnant waters), and suggest possible solutions from a series of case studies worldwide. We find that rivers in the Global South, with their distinctive geographical and socio-political setting, display significant differences from the Urban Stream Syndrome described so far in temperate zones. We introduce the term of ‘Southern Urban Hydrosystem Syndrome’ for the biophysical problems as well as the social interactions, including the perception of water bodies by the urbanites, the interactions of actors (e.g., top-down, bottom-up), and the motivations that drive urban hydrosystem restoration projects of the Global South. Supported by a synthesis of case studies (with a focus on Brazilian restoration projects), this paper summarizes the state of the art, highlights the currently existing lacunae for research, and delivers examples of practical solutions that may inform UNESCO’s North–South–South dialogue to solve these urgent problems. Two elements appear to be specifically important for the success of restoration projects in the Global South, namely the broad acceptance and commitment of local populations beyond merely ‘ecological’ justifications, e.g., healthy living environments and ecosystems with cultural linkages (‘River Culture’). To make it possible implementable/practical solutions must be extended to (often poor) people having settled along river banks and wetlands.