Under the influences of both anthropogenic activities and natural forces, saltwater intrusion has been a main issue in the Pearl River Estuary (PRE), China, in recent decades. Using long-term observation data for river channel bathymetry, hydrology, hydraulics, and meteorology, the causes and effects of the increasingly severe saltwater intrusion were investigated in this study. The worsening saltwater intrusion is characterized by an increase in salinity, prolonged and seasonally advanced duration with salinity exceeding the national standard, the extension of saltwater intrusion length and the highly stratified salinity, which can be attributed to uneven sand dredging, rising tides and changes of wind directions. Uneven sand dredging indirectly reduced the dilution capacity on the saltwater and made it difficult to discharge the saltwater. Rising tides and northeasterly migration of wind can strengthen the tidal dynamics and push saltwater further upstream. This study aims to draw attention to the issues of saltwater intrusion and offer information for the sustainable utilization of water resources for the estuaries around the world.