Phase equilibria of the ternary system (water + phosphoric acid + mesityl oxide) were investigated, and experimental tie-line data of liquid–liquid equilibrium were obtained at T = (298.2, 308.2, and 318.2) K and atmospheric pressure. The mass fractions of mesityl oxide and phosphoric acid were determined by high-performance liquid chromatography and acid–base titration, respectively. A limitation for the complete investigation of biphasic regions was observed in the (water + phosphoric acid + mesityl oxide) system, which was not detected in previous aqueous ternary systems containing mesityl oxide and other weak acids. The unsaturated carbon–carbon double bond of mesityl oxide is the cause of this limitation. Distribution coefficients (0.05 up to 0.25) and separation factors (1.05 up to 2.58) were determined over the biphasic area and proved the efficiency of mesityl oxide in the studied range. All the evaluated experimental data of the ternary system were correlated using the Hand equation to confirm the reliability of the endpoints. Temperature increments increased the extraction ability of mesityl oxide. The nonrandom two-liquid activity coefficient model was applied to correlate the measured tie-line points. Binary interaction parameters were obtained in each temperature, and temperature dependence of the parameters was investigated. The root-mean-square deviation values (less than 1% in all correlations) proved the quality of modeling, and the interaction parameters were validated. Biphasic regions were predicted using the obtained interaction parameters where experimental data could not be measured.