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The 2013-2015 drought in the Metropolitan Region of São Paulo exposed the lack of resilience of the regional water supply system, highly dependent on the Cantareira reservoirs. In this paper, inflows to each of the four main Cantareira reservoirs are tested for systematic change. Persistent trends in streamflow, rainfall, temperature and evapotranspiration are first evaluated. Streamflow was also tested for step change. Double-mass curves were employed to assess modification in the precipitation-runoff relationship. Subsequently, we used the climate elasticity method and the ABCD model to quantify the relative contribution of climate and human activities into the detected trends. Only Cachoeira and Atibainha sub-basins showed a significant downward trend in streamflow. The results for step change were also significant, and the year of occurrence coincided with breakpoints in precipitation-runoff relationship. For both Cachoeira and Atibainha, human activities had a more significant impact on streamflow reduction than climate variability. Land use and cover maps suggest that the reduction of pasture/abandoned land parallel to an increase in reforestation/silviculture is behind streamflow reduction. The results highlight the importance of coordinating land-use patterns and water management, as an important contributor beyond any considerations of a changing climate. Implications for better managing regional water resources are discussed. [ABSTRACT FROM AUTHOR]