This study presents the first regional groundwater hydrogeochemical portrait of the Bas-Saint-Laurent region (BSL), a region shaped by the Appalachians, a strong Quaternary glacial heritage, and coastal dynamics from the St. Lawrence Estuary. The proximity of BSL’s aquifers to St. Lawrence Estuary and its geological history with the past Goltwait Sea transgression create unique issues with respect to groundwater mineralization and sustainability in the region. The study is based on the distribution of major and trace elements and stable isotope signatures of water and inorganic carbon (δ18O, δ2H, δ13CDIC) in 145 groundwater samples collected in private and municipal wells distributed evenly over the study area. Groundwater shows a wide range of composition as indicated by the seven facies revealed by their composition of major elements. Ca-HCO3 and Na-HCO3 facies mainly dominate the regional groundwater composition, representing respectively 66 and 20% of the samples. Nevertheless, no significant relation between the geology, the aquifer confinement, and the geochemical facies emerged. This suggests that factors other than the hydrological settings may control the chemical composition of the groundwater in the study area. A hierarchical cluster analysis (HCA), including major, minor and trace elements, was performed, allowing the water samples to be distributed into four distinct geochemical groups that reveal a gradient from less mineralized (C4 and C2 groups with a dominant Ca-HCO3 facies) in the recharge areas to more mineralized (C1 with a Ca-HCO3 facies, to C3 with a Na-HCO3 facies) in the coastal discharge areas. Based on geochemical graphs and isotopic signatures, a conceptual model is proposed to explain this hydrogeochemical evolution at the regional scale. The most remarkable finding is that groundwater mineralization does not originate from modern seawater mixing despite the proximity of St. Lawrence seawater. Most of the hydrochemical evolution and groundwater mineralization is induced by the mixing with evaporated or remnant seawater originated from past transgressions, cation exchanges and mineral dissolution.