Carbon capture and storage (CCS) provides the opportunity to minimize atmospheric carbon emissions from fossil fuel power plants. However, CCS increases cooling water use and few studies have simulated the potential impacts of low flows on CCS power plant reliability. We present a framework to simulate the impacts of natural hydrological variability and climatic changes on water availability for portfolios of CCS capacity and cooling technologies. The methods are applied to the River Trent, the UK’s largest inland cooling water source for electricity generation capacity. Under a medium emissions climate change scenario, the projected median reductions in river flow by the 2040s was 43% for Q99.9 very low flows and 31% in licensable abstractions between Q99.9 and Q91. With CCS developments, cooling water abstractions are projected to increase, likely exceeding available water for all users by the 2030s–2040s. Deficits are reduced when wet/dry hybrid tower cooling is used, which may increase reliability at low flows. We also explore alternative water licensing regimes, currently considered by the UK Government. Climate change and growing cooling demands, individually and jointly present risks that will be prominent by the 2030s, if unaddressed. These risks may be managed if water-efficient abstraction is prioritized when supplies are limited.