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The Ganges basin provides essential water for drinking, irrigation, industrial use and power generation. Global climate change will affect the water availability in the basin and inevitably intensify the competition for water among major users, particularly from thermal power generation. Knowledge on the spatial distribution of water supply-demand gaps and the water stress for meeting the cooling water requirements is crucial for effective energy planning and water resource management. This article presents the outcomes from the India case study based on an integrated assessment of the water-energy nexus in the Ganges sub-basins focusing on water stress assessment for thermal power plants up to 2050 under climate change conditions. The results from the hydrological modelling show that the overall water availability in the four studied sub-basins, namely Chambal, Damodar, Gandak and Yamuna, will increase by 13%, 33%, 21% and 28%, respectively, in 2050 compared with the levels in 2010 under the greenhouse gas Representative Concentration Pathway (RCP) scenario 4.5. However, water availability will not be evenly distributed throughout the year and in some sub-basins water will be less available in the dry seasons. For example, Yamuna will have 25% less water in the dry season in the 2050s. Steady growth of water demand will cause serious water deficit in 30 out of 40 districts in Yamuna and 18 out of 33 districts in Gandak in 2050 under RCP 4.5. Consequently, 40% of the existing and planned thermal power plants in Damodar and almost all in Gandak and Yamuna will face high water risks in the future, endangering the energy security in India. Energy development planning and water resource management therefore need to take into account the water risks posed to future thermal power generation and consider the relocation of the planned installations from water-stressed areas (particularly Gandak) to alternative locations with water surplus (such as Chambal). It is also important to adopt less water-intensive power generation technologies and cooling systems for the planned and new installations.