Population growth and industrialization are the major factors increasing demand of water resources and posing challenge in reconciling this renewable but limited natural element. The Zayandeh Rud river basin, in central Iran, with a large domestic, agricultural and industrial water uses facing an increased complexity in managing water resources to make balance between water supply and demand. A sound knowledge of water resources availability is needed for the long-term planning and management of this basin.In this study we used the physical and semi-distributed SWAT model to simulate hydrological cycle taking into consideration of Zayandeh Rud dam operation, inter-basin water transfer projects and consumptive water use in the basin. The Sequential Uncertainty Fitting program (SUFI2) was used to calibrate and validate the two separate hydrologic model representing water situation for 1956-1970 (before construction of dam) and 1985-2005 (after construction of dam). SUFI2 is a tool for multi-site calibration and uncertainty analysis. It is capable of analyzing a large number of parameters and measured data from many gauging stations simultaneously. Its efficiency in terms of the smallest number of model runs to achieve good calibration and prediction uncertainty results is of great importance when dealing with computationally intensive, complex large-scale models. Two indices were used to quantify the goodness of calibration-uncertainty performance: the P-factor, which is the percentage of data bracketed by the 95PPU band (maximum value 100%), and the R-factor, which is the average width of the uncertainty band divided by the standard deviation of the corresponding measured variable. The measured and simulated data were compared using a criterion efficiency (br 2 ) which is modified version of coefficient of determination (r 2 ). The calibration, validation, uncertainty performances were satisfactory for the whole basin. This was different among hydrometric stations. The average annual values of P-factor, R-factor, br 2 , and r 2 for the whole basin were 0.73, 1.15, 0.53, and 0.56 for the period 1956-1970 and 0.49, 1.07, 0.57and 0.59 for the period 1985-2005. The two calibrated validated models were used to quantify all components of the water balance including blue water flow (water yield plus deep aquifer recharge), green water flow (actual and potential evapotrairation) and green water storage (soil moisture) at sub-basin level with monthly time-steps. The prediction uncertainty of the long-term average annual water resources components indicated no substantial change in the present compare to the past period. However, the averaged monthly values showed a considerable change in their spatial and temporal pattern. This is partially due to the water management projects (e.g. dam construction) and partly because of the change in temporal pattern of precipitation in the region. This study lay a basis to develop an Integrated Water Resources Management tool in the basin for advanced studies concerning water supply-demand issues as well as climate change impact and adaptation strategies and to analyze different policy options and to explore possibilities to enhance water productivity in the basin in favor of stakeholders and decision makers in near and far future. Keywords: SWAT model, Zayandeh-Rud, Calibration, Validation, Uncertainty