Karst geothermal water has attracted significant attention due to its rich geological information and substantial energy potential. This study employed δ18O, δD, and 87Sr/86Sr isotopes, along with saturation index calculation, to investigate the hydrogeochemical processes and genesis of karst geothermal water in the eastern Guanzhong Basin, China. The geothermal reservoir temperature, circulation depth, and the mixing ratio of cold and geothermal water were also determined. Results demonstrate that the geothermal water predominantly exhibits an HCO3⋅SO4⋅Cl hydrochemical type, with total dissolved solids (TDS) ranging from 685.47 to 1358.70 mg/L, primarily controlled by carbonate dissolution (calcite, dolomite) and silicate weathering. Isotopic signatures confirm meteoric precipitation as the dominant recharge source, originating from mountainous catchments at elevations of 500–800 m. The karst geothermal water in the eastern Guanzhong Basin has undergone substantial mixing with shallow groundwater during both water-rock interactions and subsurface migration processes, substantially influencing the hydrochemical properties of the geothermal water. The average mixing ratio of geothermal water and cold water was estimated from 64% to 90% using the silica enthalpy equation method. After correcting for mixing effects, SiO2 geothermometer constrains deep thermal reservoir temperatures to 88–167 °C, corresponding to circulation depths of 2157–4414 m.