Artificial neural networks (ANNs) are powerful data-oriented “black-box” algorithms capable of assessing and delineating linear and multifaceted non-linear correlations between the dependent and explanatory variables. Through the years, neural networks have proven to be effective and robust analytical techniques for establishing artificial intelligence-based tools for modelling, estimating, and projecting spatial and temporal variations in water bodies. Accordingly, ANN-based algorithms gained increased attention and have emerged as practical alternatives to traditional approaches for hydro-chemical analysis. ANNs are among the widely used computer systems for modelling surface water quality. Considering their wide recognition, resilience, flexibility, and accuracy, the current study employs a neural network-based methodology to construct a novel water quality index (WQI) model suitable for analysing South African rivers. The feed-forward, back-propagated multilayered perceptron model has three parallel-distributed neuron layers interconnected with seventy weighted links orientated laterally from left to right. First, the input layer includes thirteen neuro-nodes symbolising thirteen explanatory variables, including NH3, Ca, Cl, Chl-a, EC, F, CaCO3, Mg, Mn, NO3, pH, SO4, and turbidity (NTU). Second, the hidden layer consists of eleven neuro-nodes accountable for computational tasks. Lastly, the output layer features one neuron responsible for conveying network outcomes using a single-digit WQI rating extending from zero to one hundred, where zero represents substandard water quality and one hundred denotes exceptional water quality. The AI-based model was developed using water quality data obtained from six monitoring locations within four drainage basins under the management of the Umgeni Water Board in the KwaZulu-Natal Province of South Africa. The dataset comprises 416 samples randomly divided into training, testing, and validation sets using a proportional split of 70:15:15%. The Broyden–Fletcher–Goldfarb–Shanno (BFGS) technique was utilised to conduct backpropagation training and adjust synapse weights. The dependent variables are the WQI scores from the universal water quality index (UWQI) model developed specifically for South African river basins. The ANN demonstrated enhanced efficiency through an overall correlation coefficient (R) of 0.985. Furthermore, the neural network attained R-values of 0.987, 0.992, and 0.977 for the training, testing, and validation intervals. The ANN model achieved a Nash–Sutcliffe efficiency (NSE) value of 0.974 and coefficient of determination (R2) of 0.970. Sensitivity analysis provided additional validation of the preparedness and computational competence of the ANN model. The typical target-to-output error tolerance for the ANN model is 0.242, demonstrating an adequate predictive ability to deliver results comparable with the target UWQI, having the lowest and highest index ratings of 75.995 and 94.420, respectively. Accordingly, the three-layer neural network is scientifically sound, with index values and water quality evaluations corresponding to the UWQI results. The current research project seeks to document the processes used and the outcomes obtained.