Zayandeh-Rud river basin as one of the major industrial and demographic poles due to water supply in different parts of Isfahan and Chaharmahal-va-Bakhtiari provinces as well as the complexity of social and economic issues involved in the optimal management of water resources in the basin, today there is a severe crisis and the Irregular issues upstream - downstream. Accurate and systematic identification of hydrologic conditions and available water resources is essential for sustainable management in the basin. This makes clear the scientific and applied value of the water balance. Estimation of water balance at the river basin requires processing large amounts of spatial information therefore using GIS tools is inevitable. In the present study, the Soil and Water Assessment Tool (SWAT) a conceptual and semi-distributive model was used to simulate the water balance on the Zayandeh-Rud river basin. For this purpose, the input required data consist of digital elevation model, land use map, soil texture map and meteorological information including daily rainfall data and minimum and maximum temperature data were introduced to the model then the model was implemented with these data. Sensitive SWAT parameters Effective on stream flow were detected using the SUFI2 algorithm in SWAT-CUP program. The model was calibrated and evaluated on a monthly scale with the parameters selected in the sensitivity analysis step by Nash-Sutcliffe Efficiency (NSE) as a target function and also using the data from three hydrometric stations in the basin (Polzamankhan, Mousian and Diziche). The model was calibrated for 2000-2006 period and evaluated for 2007-2009 period. The results showed that calibrated model for Zayandeh-Rud river basin has good performance for both calibration and validation periods. Therefore, the SWAT model has acceptable performance in simulating the water balance of the Zayandeh-Rud river basin. In this study, in order to assess the impact of climate change used the GCMs model from the fifth phase of the Coupled Model Intercomparison Project (CMIP5) (under three scenarios RCP2.6, RCP4.5 and RCP8.5) that has published by IPCC. Output data from global climate models (GCMs) were introduced to the LARS-WG climate generator after spatial downscaling and future climate data was generated by this generator. The data of these models were evaluated in the historical period with observation data of the basin and assessed by the Root Mean Squared Error (RMSE) method, and then the model which corresponds to the most consistent with the observational data of each climatic parameter in each station was used to predict the future climate data. For this purpose, the base period was selected from 1971 to 2005 and the climatic data for each parameter at each station was predicted for the period 2040-2049. Finally, the effects of climate change on the water balance components including the evapotrairation, surface runoff, lateral flow, Groundwater flow, aquifer recharge, Snow fall and water yield were investigated. Among all the water balance components, the evapotrairation has the highest share of the water balance which in the future will increase 0.8mm under RCP2.6 and RCP4.5 and 0.9 mm in RCP8.5. Surface runoff will increase 11.2, 9.7 and 9.2 mm respectively in RCP2.6, RCP4.5 and RCP8.5 scenarios. The groundwater flow will increase 2.5 mm in RCP2.6 and RCP4.5 scenarios and 2.33 mm in RCP8.5 scenario. The amount of lateral flow compared with other components is negligible and there will be no significant changes between 2009 and 2049. Keywords: Water Balance, SWAT Model, SUFI2 Algorithm, Climate Change, Zayandeh-Rud River Basin