The continuous and effective monitoring of the water quality of small rural rivers is crucial for rural sustainable development. In this work, machine learning models were established to predict the water quality of a typical small rural river based on a small quantity of measured water quality data and UAV hyperspectral images. Firstly, the spectral data were preprocessed using fractional order derivation (FOD), standard normal variate (SNV), and normalization (Norm) to enhance the spectral response characteristics of the water quality parameters. Second, a method combining the Pearson’s correlation coefficient and the variance inflation factor (PCC–VIF) was utilized to decrease the dimensionality of features and improve the quality of the input data. Again, based on the screened features, a back-propagation neural network (BPNN) model optimized using a mixture of the genetic algorithm (GA) and the particle swarm optimization (PSO) algorithm was established as a means of estimating water quality parameter concentrations. To intuitively evaluate the performance of the hybrid optimization algorithm, its prediction accuracy is compared with that of conventional machine learning algorithms (Random Forest, CatBoost, XGBoost, BPNN, GA–BPNN and PSO–BPNN). The results show that the GA–PSO–BPNN model for turbidity (TUB), ammonia nitrogen (NH3-N), total nitrogen (TN), and total phosphorus (TP) prediction exhibited optimal accuracy with coefficients of determination (R2) of 0.770, 0.804, 0.754, and 0.808, respectively. Meanwhile, the model also demonstrated good robustness and generalization ability for data from different periods. In addition, we used this method to visualize the water quality parameters in the study area. This work provides a new approach to the refined monitoring of water quality in small rural rivers.