A few studies have evaluated the impact of land use land cover (LULC) change on surface water quality in the Vietnamese Mekong Delta (VMD), one of the most productive agricultural deltas in the world. This study aims to evaluate water quality parameters inside full- and semi-dike systems and outside of the dike system during the wet and dry season in An Giang Province. Multivariable statistical analysis and weighted arithmetic water quality index (WAWQI) were used to analyze 40 water samples in each seasons. The results show that the mean concentrations of conductivity (EC), phosphate (PO4 3−), ammonium (NH4 +), chemical oxygen demand (COD), and potassium (K+) failed to meet the World Health Organization (WHO) and Vietnamese standards for both seasons. The NO2 − concentration inside triple and double rice cropping systems during the dry season exceeds the permissible limit of the Vietnamese standard. The high concentration of COD, NH4 + were found in the urban area and the main river (Bassac River). The WAWQI showed that 97.5 and 95.0% of water samples fall into the bad and unsuitable, respectively, for drinking categories. The main reason behind this is direct discharge of untreated wastewater from the rice intensification and urban sewerage lines. The finding of this study is critically important for decision-makers to design different mitigation or adaptation measures for water resource management in lieu of rapid global changes in a timely manner in An Giang and the VMD