Considering the scouring depth downstream of weirs is a challenging issue due to its effect on weir stability. The adaptive neuro-fuzzy inference systems (ANFIS) model integrated with optimization methods namely cultural algorithm, biogeography based optimization (BBO), invasive weed optimization (IWO) and teaching learning based optimization (TLBO) are proposed to predict the maximum depth of scouring based on the different input combinations. Several performance indices and graphical evaluators are employed to estimate the prediction accuracy in the training and testing phase. Results show that the ANFIS-IWO offers the highest prediction performance (RMSE = 0.148) compared to other models in the testing phase, while the ANFIS-BBO (RMSE = 0.411) provides the lowest accuracy. The findings obtained from the uncertainty analysis of prediction modeling indicate that the input variables variability has a higher impact on the predicted results than the structure of models. In general, the ANFIS-IWO can be used as a reliable and cost-effective method for predicting the scouring depth downstream of weirs.