The Zayanderud River basin supports vital economic and social functions in Iran, yet faces critical water security challenges. This study employs integrated modeling to investigate how climate and land use changes impact the hydrology of the Zayanderud basin. Using SWAT model, we successfully simulated streamflow, with Nash-Sutcliffe Efficiency values of 0.58-0.71 during calibration and validation periods.. Downscaled CMIP5 projections indicate significant 21st-century warming, mainly in winter, and shifting precipitation patterns, influencing water availability. Predicted land use changes show a notable decrease in pasture area by 2060, accompanied by an increase in bare lands, as well as expansion of both rainfed and irrigated agriculture, leading to increased water demand. Through the incorporation of climate and land use projections, the SWAT model forecasts overall long-term increases in streamflow, though with expanding uncertainty reflecting heightened variability. Seasonally, there's an anticipated rise in winter flow and a decrease in summer flow. Detailed analysis of baseflow reveals similar trends, with winter peaks and summer reductions due to altered precipitation. Rising evapotranspiration due to warming and land use changes is also projected. These results underline the elevated risks of both severe low-flow periods and increased flooding. Urgent adaptive strategies are necessary to manage winter flows effectively while conserving water for drier periods to enhance resilience. This study's integration of robust hydrological modeling with climate and land use scenarios provides actionable insights for adapting the Zayanderud basin's water resources to intensifying hydroclimatic extremes under climate change. The methodologies provide transferable frameworks for sustainable water management globally.