As water scarcity puts over 80% of the world’s population at risk, water quality has become a major environmental topic. In particular, climate change has jeopardized the quality of water within the Vietnamese Mekong Delta (VMD), a key agronomic and aquaculture hub. A modest canal system and small to medium-sized reservoirs in the semi-mountain region of An Giang province contribute to a less abundant water supply and a tendency for water quality reservoirs to deteriorate. The water quality index method and descriptive technique were used in this study. The results show that in the period 2017–2020, some water quality indicators exceeded the permissible limits of the Vietnamese standards for domestic surface water in column B1 (NO3-, Total Coliform, BOD5, COD, N-NH4+) but are consistent, but are allowed for use in irrigation purposes. Findings show that for many years, WQI values in Tinh Bien and Tri Ton districts have diminished because of wastewater pollution. WQI values near the shores of O Tuk Sa Reservoir (Tinh Bien), and O Ta Soc Reservoir (Tri Ton) diminished over time. According to the WQI index, the water quality at the reservoir monitoring stations has fluctuated throughout the years, so it is advised that people implement water purification techniques for long-term well-being.