Calcite and barite are two of the most common scale minerals that occur in various geochemical and industrial processes. Their solubility predictions at extreme conditions (e.g., up to 250 °C and 1500 bar) in the presence of mixed electrolytes are hindered by the lack of experimental data and thermodynamic model. In this study, calcite solubility in the presence of high Na 2 SO 4 (i.e., 0.0407 m Na 2 SO 4 ) and barite solubility in a synthetic brine at up to 250 °C and 1500 bar were measured using our high-temperature high-pressure geothermal apparatus. Using this set of experimental data and other thermodynamic data from a thorough literature review, a comprehensive thermodynamic model was developed based on the Pitzer theory. In order to generate a set of Pitzer theory virial coefficients with reliable temperature and pressure dependencies which are applicable to a typical water system (i.e., Na-K-Mg-Ca-Ba-Sr-Cl-SO 4 -CO 3 -HCO 3 -CO 2 -H 2 O) that may occur in geochemical and industrial processes, we simultaneously fit all available mineral solubility, CO 2 solubility, as well as solution density. With this model, calcite and barite solubilities can be accurately predicted under such extreme conditions in the presence of mixed electrolytes. Furthermore, the 95% confidence intervals of the estimation errors for solution density predictions are within 4 × 10 −4 g/cm 3 . The relative errors of CO 2 solubility prediction are within 0.75%. The estimation errors of the saturation index mean values for gypsum, anhydrite, and celestite are within ±0.1 and that for halite is within ±0.01, most of which are within experimental uncertainties.