Large-scale monitoring of water quality parameters (WQPs) is one of the most critical issues for protecting and managing water resources. However, monitoring optically inactive WQPs, such as total nitrogen (TN), ammoniacal nitrogen (AN), and total phosphorus (TP) in inland waters, is still challenging. This study constructed retrieval models to explore the spatiotemporal evolution of TN, AN, and TP by Landsat 8 images, water quality sampling, and five machine learning algorithms (support vector regression, SVR; random forest regression, RFR; artificial neural networks, ANN; regression tree, RT; and gradient boosting machine, GBM) in the Nandu River downstream (NRD), a tropical river in China. The results indicated that these models can effectively monitor TN, AN, and TP concentrations at in situ sites. In particular, TN by RFR as well as AN and TP by ANN had better accuracy, in which the R² value ranged between 0.44 and 0.67, and the RMSE was 0.03–0.33 mg/L in the testing dataset. The spatial distribution of TN, AN, and TP was seasonal in NRD from 2013–2022. TN and AN should be paid more attention to in normal wet seasons of urban and agricultural zones, respectively. TP, however, should be focus on in the normal season of agricultural zones. Temporally, AN decreased significantly in the normal and wet seasons while the others showed little change. These results could provide a large-scale spatial overview of the water quality, find the sensitive areas and periods of water pollution, and assist in identifying and controlling the non-point source pollution in the NRD. This study demonstrated that multispectral remote sensing and machine learning algorithms have great potential for monitoring optically inactive WQPs in tropical large-scale inland rivers.