The purpose of this study was to develop and optimize the liquid-phase transesterification reaction of waste cooking oil with methanol over a solid base catalyst using a 3-level 4-factor Box–Behnken statistical design (BBD). New and efficient solid base SrO/MgO catalysts with different molar ratios of Sr to Mg were synthesized by the co-precipitation method followed by calcinations at 850 °C for 5 h. Techniques such as AAS, Hammett indicator procedure, CO2- TPD, SEM, FT-IR, BET and XRD were used for characterization of the catalysts. The results of the Hammett indicator procedure and CO2- TPD analysis confirm the generation of super basicity on the surface of SrO/MgO catalyst. The SrO/MgO (3:7) catalyst has higher activity in comparison with the other samples. The effects of four process-based factors including catalyst amount, temperature, methanol/oil molar ratio and reaction time on the yield of biodiesel were studied. Analysis of variance was applied to study the impacts of the main factors and their interactions. The optimized conditions (catalyst amount 0.1 g, ME/oil molar ratio 7.77, temperature 50.16 °C and reaction time 1.37 h) predicted by BBD were in great accord with the experimental results and obtained 87.49% biodiesel yield. The effect of catalyst recycling and reusability potential of synthesized catalyst samples were studied. The stability and reusability of catalysts prepared by co-precipitation method were much more than those of catalysts prepared by impregnation method.