Predicting the availability and quality of freshwater resources is a pressing concern in the Mediterranean area, where a number of agricultural systems depend solely on precipitation. This study aims at predicting streamflow and nonpoint pollutant loads in a temporary river system in the Mediterranean basin (Sulcis area, Sardinia, Italy). Monthly discharge, suspended sediment, nitrate nitrogen, total nitrogen, mineral phosphorus, and dissolved oxygen in-stream monitoring data from gauge stations were used to calibrate and validate the Soil and Water Assessment Tool model for the period 1979–2009. A Sequential Uncertainty Fitting procedure was used to auto-calibrate parameter uncertainties and model evaluation. Monthly simulation during the validation period showed a positive model performance for streamflow with Nash–Sutcliffe efficiency and percent bias values of 0.7% and 18.7%, respectively. The simulation results at a watershed level indicate that the sediment load was 1.13 t ha−1 year−1, while for total nitrogen and total phosphorus, the simulated values were 4.8 and 1.18 kg ha−1 year−1, respectively. These results were consistent with the values of soil and nutrient losses observed in the Mediterranean area, although hot-spot areas with high nutrient loadings were identified. The calibrated model could be used to assess long-term impacts on water quality associated with the simulated land use scenarios.