A significant problem in the sustainable management of water resources is the lack of funding and long-term monitoring. Today, this problem has been greatly reduced by innovative, adaptive, and sustainable learning methods. Therefore, in this study, a sample river was selected and 14 variables observed at 5 different points for 12 months, traditionally reference values, were calculated by multivariate statistical analysis methods to obtain the water quality index (WQI). The WQI index was estimated using different algorithms including the innovatively used multiple linear regression (MLR), multilayer perceptron artificial neural networks (MLP-ANN) and various machine learning estimation algorithms including neural networks (NN), support vector machine (SVM), gaussian process regression (GPR), ensemble and decision tree approach. By comparing the results, the most appropriate method was selected. The determination of water quality was best estimated by the multiple linear regression (MLR) model. As a result of this MLR modeling, high prediction performance was obtained with accuracy values of R2 = 1.0, RMSE = 0.0025, and MAPE = 0.0296. The root mean square error (RMSE), percent mean absolute error (MAE), and coefficient of determination (R2) were used to determine the accuracy of the models. These results confirm that both MLR model can be used to predict WQI with very high accuracy. It seems that it can contribute to strengthening water quality management. As a result, as with the powerful results of the innovative approaches (MLR and MLP-ANN) and other assessments, it was found that the presence of intense anthropogenic pressure in the study area and the current situation needs immediate remediation.