Changzhou is a typical industrialized city in the Yangtze River Delta. The rapid development has had a series of impacts on the groundwater environment over the years. The chemical components of groundwater are controlled by natural conditions and human activities. It needs a further study of the present situation of groundwater chemical genesis and influencing factors. Based on the analysis of the occurrence conditions of hydrogeology, this paper analyzes the chemical characteristics and genesis of groundwater at different aquifer through statistical analysis, ion ratio and principal component analysis. The results show that the main hydrochemical types of phreatic water are HCO3-—Ca2+·Mg2+, HCO3-—Ca2+ and HCO3-·Cl-—Na+·Ca2+ type, the main hydrochemical types of the first confined groundwater are HCO3-—Na+·Ca2+ and HCO3-—Ca2+ type, the main hydrochemical types of the second and third confined groundwater is HCO3-—Na+·Ca2+ type. From shallow layer to deep layer, the alkalinity of groundwater increases gradually, the mean value of TDS content decreased, hydrochemical types have changed from pluralism to singleness. The chemical composition of groundwater is mainly affected by mineral dissolution, cation alternating adsorption and human activities. The chemical genesis of phreatic water and the first confined groundwater is mainly controlled by the dissolution of carbonate, silicate, evaporated rock salt and sulfate minerals, and they are significantly affected by human activities. The second and third confined groundwater are obviously affected by the dissolution of carbonate and silicate minerals and cation exchange. Human activities have little impact on deep groundwater.