The moving of manufacturing industry from developed countries to Dongguan, China, promoted the semi-urbanization and rural industrialization in this area. It is urgent to acquire the impact of the enhanced anthropogenic pressure on the evolution of groundwater chemistry in this area. The objectives, in this study, were to understand the evolution of groundwater chemistry in Dongguan area based on the comparison of hydrochemical data variations and land use changes during the urbanization, to distinguish the impact of natural processes and anthropogenic activities on the groundwater chemistry by using principal components analysis (PCA) and hierarchical cluster analysis (HCA), and to discuss the origins of trace elements in groundwater. Eighteen physico-chemical parameters were investigated at 73 groundwater sites during July 2006. By analyzing the hydrochemical data, it shows that lateral flow from rivers and agricultural irrigation are the mechanisms controlling the groundwater chemistry in the river network area where the cation exchange of Na+ in sediments taken up by the exchanger Ca2+ occurs. Seawater intrusion is the mechanism controlling the groundwater chemistry in the coast area where the cation exchange of Ca2+ in sediments taken up by the exchanger Na+ occurs. The ion exchange reaction for fissured aquifer is weak in the study area. In addition, the comparison of hydrochemical data between in 2006 and in 1980 shows that anthropogenic activities such as excessive application of agricultural fertilizers, inappropriate emissions of domestic sewage and excessive emissions of SO2 are responsible for the occurrences of groundwater with NO3−, SO42− and Mg2+ types. Four principal components (PCs) were extracted from PCA, which explain 80.86% of the total parameters in water chemistry: PC1, the seawater intrusion and As contamination; PC2, the water–rock interaction, surface water recharge and acidic precipitation; PC3, heavy metal pollution from industry; and PC4, agricultural pollution and sewage intrusion. Four clusters were generated from HCA: cluster 1 is mainly influenced by the industrialization; cluster 2 is mainly affected by the water–rock interaction and the irrigation and lateral flow of river water; cluster 3 is mainly influenced by the seawater intrusion; and cluster 4 is mainly influenced by the sewage intrusion and agricultural pollution. The results show that both natural processes such as seawater intrusion, water–rock interaction and lateral flow of river water and anthropogenic activities such as industrialization, sewage intrusion and agricultural pollution are the two major factors for the evolution of groundwater chemistry in Dongguan area.