Groundwater serves as an important resource for people in the Mekong Delta, but its quality has been continuously declined from human activities. Current status of the groundwater quality needs to be evaluated for sustainable groundwater resource management. This study aimed to evaluate the groundwater quality for drinking purposes in the Mekong Delta, Vietnam, using multivariate statistical methods and integrated-weight water quality index. Data comprised 8 water quality parameters (pH, total hardness, nitrate (NO3-), iron (Fe), lead (Pb), mercury (Hg), arsenic (As), and coliforms) obtained from 64 observation wells in An Giang province, Dong Thap province, and Can Tho city, were analyzed by cluster analysis (CA), principal component analysis (PCA), and integrated-weight water quality index (IWQI). The results indicated that most parameters were within standards while excessive hardness and Fe contamination were found in some regions. More than 80% of samples were detected with serious coliform contamination. The CA results revealed that groundwater quality heavily depend on geological locations with 4 clusters of the sampling locations. Three principal components obtained from PCA could explain 77.2% of the groundwater quality variation. The IWQI values ranging from 4 to 2761 classified groundwater quality as excellent (53.1%), good (25%), poor (9.4%), very poor (4.7%), and undrinkable (7.8%), which were associated with coliform contamination. These findings have provided insights into the groundwater quality status in the region, which can benefit in developing a water protection strategy.