This paper compares the drivers and barriers to urban wastewater treatment in India and Brazil. The analysis of various different cities focuses on energy efficiency and reuse of treated wastewater. Drawing on 60 semi-structured interviews in Brazil and 20 semi-structured interviews in India, the paper finds that the wastewater systems in both countries are still largely in a situation of lock-in, although innovative initiatives that focus on more resource-footprint, lifecycle-oriented approaches exist in some niche sectors. A combination of specific institutional changes and external triggers has the potential to break the lock-in. Pricing, mandatory regulations and standard setting present helpful instruments to advance institutional change, while a high number of stakeholders, vested interests and economic benefits of the status quo block it. Urbanization and land and water scarcity have been identified as external triggers for shifts in the dominant mindsets towards more sustainable solutions in both countries. For governance of the water–energy–food nexus, this paper finds that using less abstract concepts and language will increase the acceptance of the idea among local stakeholders. Additionally, cross-sectoral integration needs to be tailor-made and well-timed; immediate, full integration is not always the best option.