A process-controlled synergistic solvent extraction (SSX) system consisting Mextral EOL (β-diketone derivative) and Cyanex 923 (mixture of four alkyl phosphine oxides) has been developed for the extraction of lithium from borate and sodium rich wastewaters induced by boron industry. In order to determine regression models and determine optimum conditions, a D-optimal experimental plan was created. Reduced cubic models were chosen for all lithium and sodium extraction studies. Accordingly, the most negative effect in lithium extraction was the aqueous phase/organic phase ratio (A/O), while the pH was the most positively effective parameter. Mextral EOL had no effect on sodium extraction. Notably, it was found that Mextral EOL and Cyanex 923 had up to 1.6 times synergistic effect on lithium extraction. In optimization, the sodium extraction efficiency is minimized while the lithium yield is maximized. Three different optimization criteria were determined in each wastewater and three different optimum alternatives were established. Accordingly, the highest lithium yield was predicted to be above 91.0% and sodium yield was below 4.70%. In back-extraction studies, water and different concentrations of HCl acid solutions were used as scrubbing and stripping agents. As a result, the Mextral EOL/Cyanex 923/Kerosene SSX system has been proven to be an effective method for maximizing lithium extraction from borate-rich wastewaters and for minimizing sodium extraction.