Groundwater is a primary freshwater source for various domestic, industrial and agricultural purposes, especially in coastal regions where there are lacking surface water supply. However, groundwater quality in coastal regions is often threatened by seawater intrusion and contamination due to both anthropogenic activities and natural processes. Therefore, insights into groundwater geochemistry and occurrences are necessary for sustainable groundwater management in coastal regions. The main aim of this study is to investigate the hydrogeochemical characteristics and their influencing factors in a coastal area of the Mekong Delta, Vietnam (MD). A total of 286 groundwater samples were taken from shallow and deep aquifers for analyzing major ions and stable isotopes. The results show that deep groundwater is dominated by Ca-HCO[Formula: see text], Ca-Na-HCO[Formula: see text], Ca-Mg-Cl, and Na-HCO[Formula: see text] while shallow groundwater is dominated by the Na-Cl water type. In this region, the main geochemical processes controlling groundwater chemistry are ion exchanges, mineralization and evaporation. Groundwater salinization in coastal aquifers of the Mekong Delta is caused by (1) paleo-seawater intrusion and evaporation occurring in the Holocene and Pleistocene aquifers, (2) dissolution of salt sediment/rock and leakage of saline from upper to lower aquifers due to excessive groundwater exploitation and hydraulic connection. High nitrate concentrations in both shallow and deep aquifers are related to human activities. These results imply that groundwater extraction may exacerbate groundwater quality-related problems and suitable solutions for sustainable groundwater management in the coastal area of the Mekong Delta are needed.