The intensification of anthropogenic activities (agriculture, industry, and exploitation of water resources) during urbanization has posed significant challenges to the aquatic environment, particularly in karst regions. Karst aquifers are highly susceptible to surface contaminants and exhibit minimal natural remediation capabilities. Our understanding of the anthropogenic activities involved in these sensitive karst systems remains limited. To address this gap, we conducted a comprehensive study, collecting 285 groundwater samples in Feicheng, northern China, from 1996 to 2015. The overexploitation of karst groundwater has resulted in several concerns. The whole dataset was classified into four groups according to land use. Water quality assessments revealed a yearly decline, particularly in industrial and agricultural areas. The water chemistry transitioned from Ca-Mg-HCO3 to Ca-Mg-HCO3-SO4. Such evolution was attributed to natural hydrogeochemical processes, atmospheric precipitation, and anthropogenic inputs. Natural factors included water-rock interactions (the mineral dissolution) and ion exchange. Absolute principal component scores with multiple linear regression (APCS-MLR) were used to quantitatively estimate the sources of pollution. The results showed that hydrogeological settings (recharge, runoff, and discharge) were crucial in the hydrochemistry evolution of karst groundwater systems. In agricultural areas, it is recognized that much of the NO3− accumulation in aquifers came from upstream inputs in the groundwater system, not just irrigation and fertilization. Urban areas were affected by Cl− pollution, primarily due to domestic waste. Industrial regions of recharge zones were more susceptible to atmospheric precipitation and industrial waste, with pollutants infiltrating through rainfall and degrading water quality. Mining areas exhibit higher SO42− and lower pH due to the oxidation of sulfur-containing minerals. Therefore, the rapid response and low self-purification capacity of groundwater in karst regions necessitate caution in urban planning to mitigate impacts on these fragile systems.