Groundwater plays a leading role in ecological environment protection in semi-arid regions. The Huangshui River Basin is located in the Tibetan Plateau and Loess Plateau transition zone of semi-arid areas. Its ecological environment is relatively fragile, and there is an urgent need for systematic study of the basin to develop a groundwater environment and realize the rational and efficient development of water resources. In this study, methodologically, we combined the following: 1. Field sampling (271 groundwater samples across the basin’s hydrogeological units); 2. Comprehensive laboratory analysis of major ions and physicochemical parameters; 3. Multivariate statistical analysis (Pearson correlation, descriptive statistics); 4. Geospatial techniques (ArcGIS kriging interpolation); 5. Hydrochemical modeling (Piper diagrams, Gibbs plots, PHREEQC simulations). Key findings reveal the following: 1. Groundwater is generally weakly alkaline (pH 6.94–8.91) with TDS ranging 155–10,387 mg/L; 2. Clear spatial trends: TDS and major ions (Na⁺, Ca²⁺, Mg²⁺, Cl⁻, SO₄²⁻) increase along flow paths; 3. Water types evolve from Ca-HCO₃-dominant (upper reaches) to complex Ca-SO₄/Ca-Cl mixtures (lower reaches); 4. Water–rock interactions dominate hydrochemical evolution, with secondary cation exchange effects; 5. PHREEQC modeling identifies dominant carbonate dissolution (mean SIcalcite = −0.32) with localized evaporite influences (SIgypsum up to 0.12). By combining theoretical calculations and experimental results, this study reveals distinct hydrochemical patterns and evolution mechanisms. The groundwater transitions from Ca-HCO₃-type in upstream areas to complex Ca-SO₄/Cl mixtures downstream, driven primarily by dissolution of gypsum and carbonate minerals. Total dissolved solids increase dramatically along flow paths (155–10,387 mg/L), with Na⁺ and SO₄²⁻ showing the strongest correlation to mineralization (r > 0.9). Cation exchange processes and anthropogenic inputs further modify water chemistry in midstream regions. These findings establish a baseline for sustainable groundwater management in this ecologically vulnerable basin.