Groundwater quality appraisal is one of the most crucial tasks to ensure safe drinking water sources. Concurrently, a water quality index (WQI) requires some water quality parameters. Conventionally, WQI computation consumes time and is often found with various errors during subindex calculation. To this end, 8 artificial intelligence algorithms, e.g., multilinear regression (MLR), random forest (RF), M5P tree (M5P), random subspace (RSS), additive regression (AR), artificial neural network (ANN), support vector regression (SVR), and locally weighted linear regression (LWLR), were employed to generate WQI prediction in Illizi region, southeast Algeria. Using the best subset regression, 12 different input combinations were developed and the strategy of work was based on two scenarios. The first scenario aims to reduce the time consumption in WQI computation, where all parameters were used as inputs. The second scenario intends to show the water quality variation in the critical cases when the necessary analyses are unavailable, whereas all inputs were reduced based on sensitivity analysis. The models were appraised using several statistical metrics including correlation coefficient (R), mean absolute error (MAE), root mean square error (RMSE), relative absolute error (RAE), and root relative square error (RRSE). The results reveal that TDS and TH are the key drivers influencing WQI in the study area. The comparison of performance evaluation metric shows that the MLR model has the higher accuracy compared to other models in the first scenario in terms of 1, 1.4572*10–08, 2.1418*10–08, 1.2573*10–10%, and 3.1708*10–08% for R, MAE, RMSE, RAE, and RRSE, respectively. The second scenario was executed with less error rate by using the RF model with 0.9984, 1.9942, 3.2488, 4.693, and 5.9642 for R, MAE, RMSE, RAE, and RRSE, respectively. The outcomes of this paper would be of interest to water planners in terms of WQI for improving sustainable management plans of groundwater resources.