In the present study, the amount of nitrate and phosphate leaching from agricultural lands into the Zanjanrood River in Iran was simulated using the Soil & Water Assessment Tool (SWAT) model. The measured average monthly discharges at the Sarcham station were used to calibrate and validate the SWAT model, and the SWAT Calibration and Uncertainty Program (SWAT-CUP) model was applied to perform the uncertainty and sensitivity analyses. Three scenarios for the irrigation methods and five for the fertilizer rates were defined. The p-factor and r-factor were used for the uncertainty analysis, and two statistical indices of the coefficient of determination (R2) and Nash-Sutcliffe efficiency (NS) were utilized in the validation model. For the calibration of the monthly runoff at the basin’s outlet, the coefficients of r-factor, p-factor, R2, and NS were obtained as 0.27, 0.11, 0.83, and 0.53, respectively. The results showed that by increasing the pressurized irrigation areas, the nitrate and phosphate pollutions in the river basin were not significantly affected. With regard to fertilizer rates, by reducing the consumption of urea and phosphate fertilizers up to 50%, the amount of nitrate and phosphate leaching into the Zanjanrood River was reduced up to 16.7% and 19.2%, respectively. On the other hand, an increase of 50% in fertilizer application increased nitrate and phosphate leaching into the river by 17.2% and 17.7%, respectively. In addition, by reducing the fertilization rate and preventing unnecessary fertilization by farmers, the pollution of water resources can be largely prevented.