The Mekong Delta produces about 70 % of Vietnam's national aquaculture output, and water quality management is a key factor in maintaining high levels of production and profitability. Effective water management strategies depend on understanding the spatial and temporal variations in water quality along major waterways. Therefore, this study aimed to assess the spatial and temporal fluctuation of water quality in the waterways of five provinces with intensive aquaculture operations in the Mekong Delta. The study sites included two inland provinces (An Giang and Can Tho) where striped catfish, Pangasianodon hypophthalmus (Sauvage, 1878), is farmed, and three coastal provinces (Soc Trang, Bac Lieu, and Ca Mau) where white leg shrimp, Litopenaeus vannamei (Boone, 1931), and black tiger shrimp Penaeus monodon Fabricius, 1798, are cultured. At each sampling site, physicochemical parameters were monitored for 12 months on the main rivers which supply water to aquaculture systems. Water quality data were analysed and compared based on the coefficient of variation (CV), Pearson correlation coefficients to identify relationships among variables and principal component analysis (PCA) to identify 2–3 key parameters having the most significant influence on spatial and temporal variation in water quality in each province. BOD, COD, PO4 3-, S2-, NO2 - and NO3 - were highly variable (CV 40–120 %). Significant interrelationships ranged from -0.5 to 0.5 between many water quality parameters. Overall, water in most provinces was considered polluted. However, the water quality parameters, except for S2- and NO2 - , were within acceptable levels specified by National Technical Regulation on Surface Water Quality for Protection of Aquatic Life.