Introduction Land use and land cover (LULC) changes, and consumptive water uses are widely recognized as key drivers of alterations in basin hydrology, potentially reducing ecosystem services and threatening water security. However, the magnitude of the impacts varies strongly among basins, and many times are hidden by climate variability. In this context, this study aims to analyze the impacts that LULC changes combined with water consumption have on water availability of the Paraopeba River Basin, a strategic water supply basin of Brazil, through a scenario-based hydrological modeling framework that enables the explicit attribution of hydrological changes to anthropogenic drivers.Methods Differences in water yield were calculated through hydrological modeling considering two different scenarios: The current scenario (CS), based on LULC changes over the period 1985-2018 and averaged water consumption over the period 1985-2018; and the hypothetical scenario S1, which assumes no changes in land uses and human consumption since 1985.Results and discussion Results indicate that the S1 scenario presents higher minimum streamflows, with increases of up to 33% compared to the CS scenario. The difference in the flow-duration-curves signatures indicates that the streamflow regime has been modified because of the increase in urban and silviculture areas and human water consumption. In general, larger native vegetation areas are associated with higher evapotranspiration and canopy interception losses. Given the intense and increasing water use in the basin, current trends are likely to intensify water conflicts, threaten water security for a large population, and generate downstream impacts, including on basins that supply water to Brazil's semiarid regions.