The Mudan River Watershed, located in the northernmost region of China, is an important component of the Songhuajiang River System. The water quality of this watershed is of great importance because it is widely used for aquaculture production, hydraulic electro-generating, recreation, fishing, and irrigation. In this study, the water quality index (WQI) and principal component analysis (PCA) were employed to evaluate the Spatio-temporal variations in the surface water quality of the watershed. Ten monitoring sections were selected and monitored monthly for this study. Results indicated that the Chaihe bridge section exhibited the worst water quality with a WQI score of 32.81 due to large quantities of sewage discharge. Moreover, the water quality of the Mudan River Watershed showed seasonal variations. The WQI scores in the rainy season, non rainy season, and icebound season were 69.38, 70.99, and 41.96, which was due to the surface water runoff in the rainy season as well as the low temperature and bacterial activity in the icebound season. Furthermore, the PCA technique revealed that permanganate index and ammonia nitrogen were the primary contaminants of this watershed regardless of the season. Therefore, it is urgent to restore the water quality of the Mudan River Watershed by adopting powerful management measures and improvement methods.