Climate change is rapidly altering the global water cycle, exposing vulnerabilities in both social and environmental systems. However, uncertainty in future climate predictions makes it difficult to design and evaluate strategies for building climate resilience. In regions such as California, characterized by stressed water-supply systems, high natural climate variability, and substantial uncertainty in future precipitation projections, alternative approaches to assessing climate risks may be useful. Here, we develop a hydrologic sensitivity approach to estimate regional streamflow responses to climate change in California. We use statistical models to predict monthly streamflow from physical catchment features and evaluate how flow changes with incremental changes in precipitation and temperature. The results indicate unique regional and monthly flow responses to climate change, with early summer flows (May - July) in interior mountain region having the greatest sensitivity to temperature and winter flow (December - March) in the xeric region having the greatest sensitivity to precipitation. When evaluated over the range of global climate model projections for mid-century (2040-2069), models generally suggest shifts in streamflow regimes towards higher wet season flows and lower dry season flows relative to historical conditions. The sensitivity analysis provides insight into catchment- and regional-scale hydrologic responses in California and complements other approaches for understanding the consequences of climatic change for water and risk management.