Rivers in karst areas face increased risks from persistent growth in human activity that leads to changes in water chemistry and threatens the water environment. In this study, principal component analysis (PCA), ion ratio measurements, and other methods were used to study the water chemistry of the Qingshuijiang River Basin over the past 10 years. The results showed that the main ions in the river were Ca2+ and HCO3–, with a cation order of Ca2+ (mean: 0.93 mmol/L) > Mg2+ (mean: 0.51 mmol/L) > Na+ (mean: 0.30 mmol/L) > K+ (mean: 0.06 mmol/L) and HCO3– (mean: 2.00 mmol/L) > SO42– (mean: 0.49 mmol/L) > Cl– (mean: 0.15 mmol/L) > NO3– (mean: 0.096 mmol/L) > F– (mean : 0.012 mmol/L). In the past 10 years, the concentration of major ions in the river water in the basin has increased significantly. The weathering input of rock (mainly upstream carbonate) was the main source of Mg2+, Ca2+, and HCO3−, though sulfuric acid was also involved in this process. While K+ and Na+ were affected by the combination of human activity and the weathering input of silicate rock in the middle and lower reaches of the river, human activity was the main source of SO42−, NO3−, and F− ions. Irrigation water quality and health risks were evaluated by calculating the sodium adsorption ratio (SAR), soluble sodium percentage (Na%), residual sodium carbonate (RSC), and hazard quotient (HQ). The findings indicated that the river water was generally safe for irrigation and drinking, and the health risks were gradually reduced over time. However, long-term monitoring of the river basin is still essential, especially for the risk of excessive F− in a few tributaries in the basin.