Climate change affects the global water cycle and has the potential to alter water availability for food-energy-water production and the ecosystems services on regional and local scales. In southeastern Brazil, the Cantareira Water Supply System reached unprecedented low levels in January 2015 compromising the water supply for the Metropolitan Region of São Paulo (MRSP). However, there is still few studies investigating the effects of climate change on water availability in this region. Here, we assess the influence of climate change on water availability in the Jaguari Basin, Southeastern Brazil using a modeling approach. This basin covers and area of about 1200 km2 and it is the main source of the Cantareira Water Supply System, responsible for providing water for about 7 million people in the MRSP. To evaluate climate change scenarios, we use the lumped conceptual HYMOD model on daily time step. This model was calibrated and evaluated using daily observed data of precipitation, evapotranspiration, and discharge for the period of 1990 to 2009. To evaluated climate change scenarios, we used data of an ensemble of 17 General Circulation Models (GCMs), downscaled by MarkSim GCM working off a 30 arc-second climate surface spatial resolution forced by two Representative Concentration Pathways (RCP): RCP 4.5 and RCP 8.5. These data were integrated into the HYMOD to projected scenarios (up to 2095) of water discharge. We find values of Nash-Sutcliffe Efficiency Coefficient (NSE) and Coefficient of Determination (R2) greater than 0.80 for the calibration and evaluation period. We also noticed an increase in the peak of runoff and a decrease and baseflow for both scenarios. Such changes reflect in a higher interannual variability, therefore, increasing the risk of drought and flood. In terms of Environmental Flow Requirement, the probability of exceedance Q90, reveal a clear pattern of decreasing, about 23% from 2010 to 2040, and reaching 28% by the end of the century. Our findings indicate that the water discharge could not be enough for the current and future water demand. Our results expose the fragility of the studied basin, presenting a technical and scientific information focusing on guiding the plans and strategies to deal with situations of water scarcity.