The Qinglian River plays a significant role in China’s national water conservation security patterns. To clarify the relationship between hydrogeochemical properties and groundwater quality in this karst-fissure aquifer system, drilling data, hydrochemical parameters, and δ2H and δ18O values of groundwater were analyzed. Multiple indications (Piper diagram, Gibbs diagram, Na+-normalized molar ratio diagram, chloro-alkaline index 1, mineral saturation index, and principal component analysis) were used to identify the primary sources of chemicals in the groundwater. Silicate weathering, oxidation of pyrite and chlorite, cation exchange reactions, and precipitation are the primary sources of dissolved chemicals in the igneous-fissure water. The most relevant parameters in the karst water are possibly from anthropogenic activities, and other chemicals are mostly derived from the dissolution of calcite and dolomite and cation exchange reactions. Notably, the chemical composition of the deep karst water from the karst basin is mainly influenced by the weathering of carbonate and cation exchange reactions and is less affected by human activities. The hydrogeochemical properties of groundwater in the karst hyporheic zone are influenced by the dissolution of carbonates and silicates, evaporation, and the promotion effect of dissolution of anorthite or Ca-containing minerals. Moreover, the smallest slope of the groundwater line from the karst hyporheic zone among all groundwater groups revealed that the mixing effects of evaporation, isotope exchange in water–rock interaction or deep groundwater recharge in the karst hyporheic zone are the strongest. The methods used in this study contribute to an improved understanding of the hydrogeochemical processes that occur in karst-fissure water systems and can be useful in zoning management and decision-making for groundwater resources.