The assessment of water quality has drawn much attention due to its implications in identifying pollution sources and enhancing living environments. We currently lack a systematic understanding of spatiotemporal water quality variations and their drivers in the Yellow River Basin. Therefore, we investigated the spatial and temporal fluctuations in water parameters and the possible factors driving these changes in the watershed. Rescaled range analysis, Pearson correlation test, and a generalized linear model were employed. Over the last 13 years, the permanganate index (CODMn) and ammonia nitrogen (NH3-N) have declined at rates of 0.26 and 0.18 (mg L-1) year-1, respectively, whereas the dissolved oxygen has increased at a rate of 0.19 (mg L-1) year-1. The effective control of CODMn (94.27%) and NH3-N (96.30%) is vital to reduce pollutant discharge and increase ecological protection and restoration. Geographically, the middle reaches had poor water quality and showed a significant positive correlation between NH3-N and coal reservation ( r = 0.89; P < 0.05). The total nitrogen concentrations followed increasing spatiotemporal trends, which may be indicative of the deterioration of major water quality parameters in the near future. Our findings offer insights into the spatiotemporal variations in water quality and the factors driving these changes in the Yellow River Basin. These results can help establish theoretical references for water quality protection and management.