The deterioration signs of water quality in the Hau River are apparent. The present study analyzed the surface water quality of the Hau River using multivariate statistical techniques, including principal component analysis (PCA) and Cluster Analysis (CA). Eleven water quality parameters were analyzed at 19 different sites in An Giang and Can Tho Provinces for 12 months from January to December 2019. The findings show high levels of Biological Oxygen Demand (BOD), Total Soluble Solids (TSS), and total coliform, all year round. The PCA revealed that all the water quality parameters influenced the water quality of the Hau River, hence the relevance for water sample scrutiny. The dendrogram of similarity between sampling sites showed a maximum similarity of 95.6%. The Accumulation Factor (AF) trend showed that the concentrations/values of TSS, BOD, and phosphate (PO43−) in the downstream were 1.29, 1.53, and 1.52 times, respectively, greater than the upstream levels. Despite most of the parameters analyzed supporting aquaculture production, caution is needed in the regulation of pollution point sources to undertake sustainable aquaculture production.