Basin-scale simulation is fundamental to understand the hydrological cycle, and in identifying information essential for water management. Accordingly, the Soil and Water Assessment Tool (SWAT) model is applied to simulate runoff in the semi-arid Tambo River Basin in southern Peru, where economic activities are driven by the availability of water. The SWAT model was calibrated using the Sequential Uncertainty Fitting Ver-2 (SUFI-2) algorithm and two objective functions namely the Nash-Sutcliffe simulation efficiency (NSE), and coefficient of determination (R2) for the period 1994 to 2001 which includes an initial warm-up period of 3 years; it was then validated for 2002 to 2016 using daily river discharge values. The best results were obtained using the objective function R2; a comparison of results of the daily and monthly performance evaluation between the calibration period and validation period showed close correspondence in the values for NSE and R2, and those for percent bias (PBIAS) and ratio of standard deviation of the observation to the root mean square error (RSR). The results thus show that the SWAT model can effectively predict runoff within the Tambo River basin. The model can also serve as a guideline for hydrology modellers, acting as a reliable tool.