© 2022 by the authors.In this study, the Acısu Basin—viz., the headwater of the Gediz Basin—in Turkey, was modelled using three types of hydrological models and three different calibration algorithms. A well-known lumped model (GR4J), a commonly used semi-distributed (SWAT+) model, and a skillful distributed (mHM) hydrological model were built and integrated with the Parameter Estimation Tool (PEST). PEST is a model-independent calibration tool including three algorithms—namely, Levenberg Marquardt (L-M), Shuffled Complex Evolution (SCE), and Covariance Matrix Adoption Evolution Strategy (CMA-ES). The calibration period was 1991–2000, and the validation results were obtained for 2002–2005. The effect of the model structure and calibration algorithm selection on the discharge simulation was evaluated via comparison of nine different model-algorithm combinations. Results have shown that mHM and CMA-ES combination performed the best discharge simulation according to NSE values (calibration: 0.67, validation: 0.60). Although statistically the model results were classified as acceptable, the models mostly missed the peak values in the hydrograph. This problem may be related to the interventions made in 2000–2001 and may be overcome by changing the calibration and validation periods, increasing the number of iterations, or using the naturalized gauge data.