The development of residential areas in the trend of urbanization and the development of industrial parks and clusters have caused risks to reduce the surface water quality of the Mekong River in An Giang province. This study was conducted by sampling surface water affected by urban areas and affected by industrial parks/clusters (seven sampling points) in June 2021 and analyzing the parameters of temperature, pH, DO, TSS, COD, BOD5, N-NO3-, N-NH4+, P-PO43-, Coliform, As, Pb, Hg, Benzene hexachloride, Dieldrin. The analytical results of water samples were compared with the National Technical Regulation of Vietnam. The water quality index was calculated according to the technical guidelines of the Vietnam Environment Administration (VN_WQI). The results show that domestic and industrial wastewater has polluted the surface water of the Tien River and the Hau River, two important rivers of the downstream Mekong River, flowing through An Giang province. The pollution shows in parameters of TSS, DO, BOD5, COD, N-NH4+, and Coliform that exceeds allowable limits. However, other parameters such as temperature, pH, N-NO3-, P-PO43- are mostly at the acceptable range and within allowable limits. Based on the WQI, most of the water quality at the sampling points is poor. Therefore, it is recommended that people not directly use the Tien River and Hau River water in An Giang for drinking and domestic purposes. It is necessary to apply appropriate water treatment measures. In the coming time, authorities need to monitor and take appropriate measures to treat and manage wastewater from urban areas and industrial parks/clusters.