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Climate change affects the global water cycle and has the potential to alter water availability for food–energy–water production, and for ecosystems services, on regional and local scales. An understanding of these effects is crucial for assessing future water availability, and for the development of sustainable management plans. Here, we investigate the influence of anticipated climate change on water security in the Jaguari Basin, which is the main source of freshwater for 9 million people in the São Paulo metropolitan region (SPMR). First, we calibrate and evaluate a hydrological model using daily observed data, obtaining satisfactory coefficient of determination and Kling–Gupta efficiency values for both periods. To represent possible climate change scenarios up to 2095, we consider two International Panel on Climate Change (IPCC) Representative Concentration Pathways (RCP4.5 and RCP8.5) and use an ensemble of future projections generated by 17 general circulation models (GCMs). These data were used to drive the hydrological model to generate projected scenarios of streamflow. We then used indicators of water scarcity and vulnerability to carry out a quantitative analysis of provision probability. Our results indicate that streamflow can be expected to exhibit increased interannual variability, significant increases in flow rate between January and March, and a 2-month extension of the hydrological dry season (currently June to September) until November. The latter includes a more than a 35 % reduction in streamflow during September through November (with a > 50 % reduction in October). Our findings indicate an increased risk of floods and droughts accompanied by an expansion of the basin critical period, and our analysis of the water security indices identifies October and November as the most vulnerable months. Overall, our analysis exposes the fragility of water security in the São Paulo metropolitan region, and provides valuable technical and scientific information that can be used to guide regional plans and strategies to cope with potential future water scarcity.