To better understand the origin of the saline groundwater in the Pearl River Delta (PRD), China, water samples were collected from local aquifers, rainfall regions and rivers for isotopic and hydrochemical analysis. The hydraulic connections between the aquifers in the study area were tested by analyzing a series of water samples from different months in one hydrological year (January 2017–January 2018). The total dissolved solids (TDS) results show that the highly saline groundwater only occurs in the granites, which indicates that the TDS distribution depends on the permeability of the aquifer material. Variations in the TDS and stable hydrogen and oxygen isotope ratios (δ²H and δ¹⁸O, respectively) of the water samples from different months reflect a dynamic balance among evaporation and precipitation in a hydrological year. Additionally, the very old radiocarbon (¹⁴C) ages and undetectable amounts of tritium (³H) in most of the groundwater samples suggest that the residence time of the groundwater in the aquifer is high. In general, the saline groundwater (TDS >5 g/L) in the area mainly originated primarily from seawater intrusion in the past. Meanwhile, the water contents of saline groundwater were affected by evaporation and long-term geochemical processes, such as water-rock, sulfate reduction, methanogenesis and ion exchange. The fresh groundwater in the area is from modern meteoric precipitation recharge.