The removal efficiencies for chemical oxygen demand (COD), ammoniacal nitrogen (NH3–N), and color, as well as ozone consumption (OC) from the Malaysian semi-aerobic landfill stabilized leachate using ozone reactor, were investigated. Central composite design with response surface methodology was applied to evaluate the interaction and relationship between operating variables (i.e., ozone dosage, COD concentration, and reaction time) and to develop the optimum operating condition. Based on statistical analysis, Quadratic models for the four responses (COD, NH3–N, color, and OC) proved to be significant with very low probability values (<0.0001). The obtained optimum conditions were 70 g/m3 ozone, 250 mg/l COD, and 60 min reaction time. The results obtained by the predicted model were 26.7, 7.1, and 92 % removal for COD, NH3–N, and color, respectively, with 9.42 (kgO3/kg COD) OC. The predicted results fitted well with the results of the laboratory experiment.