The Sai Gon and Dong Nai Rivers are important for the social and economic development of Southern Vietnam. They also serve as crucial water supply sources for Ho Chi Minh City and its surrounding provinces. The objectives of the present study are to evaluate the surface water quality of these rivers and to detect the possible sources of pollutants between 2015 and 2019. The study utilized various methods, including single factor evaluation, water quality index (WQI), and principal component analysis (PCA). Water quality data, such as pH, dissolved oxygen (DO), chemical oxygen demand (COD), biochemical oxygen demand (BOD5), ammonia (N-NH4 +), phosphate (P-PO4 3-), and Coliform, from eight monitoring sites along the rivers were used for the evaluation. The results stated that the water quality of the study region generally varied from ‘moderate’ to ‘good’ and had a decreasing trend from the upstream to the downstream during the study period. In addition, PCA results indicated that domestic sewage and industrial wastewater were significant factors affecting water quality in the middle stream of the rivers. The findings of this study can be used by local environmental management authorities to gain insights into water pollution and propose potential solutions for better protection and management of water resources.