With the rapid development of the economy and the demands of people’s lives, the usage amount of polymer materials is significantly increasing globally. Chlorobenzenes (CBS) are widely used in the industrial, agriculture and chemical industries, particularly as important chemical raw materials during polymers processes. CBS are difficult to remove due to their properties, such as being hydrophobic, volatile and persistent and biotoxic, and they have caused great harm to the ecological environment and human health. Electrochemical oxidation technology for the treatment of refractory pollutants has been widely used due to its high efficiency and easiness of operation. Thus, the electrochemical oxidation system was established for the efficient treatment of monochlorobenzene (MCB) waste gas. The effect of a single factor, such as anode materials, cathode materials, the electrolyte concentration, current density and electrode distance on the removal efficiency (RE) of MCB gas were first studied. The response-surface methodology (RSM) was used to investigate the relationships between different factors’ conditions (current density, electrolyte concentration, electrode distance), and a prediction model was established using the Design-Expert 10.0.1 software to optimize the reaction conditions. The results of the one-factor experiments showed that when treating 2.90 g/m3 MCB gas with a 0.40 L/min flow rate, Ti/Ti4O7 as an anode, stainless steel wire mesh as a cathode, 0.15 mol/L NaCl electrolyte, 10.0 mA/cm2 current density and 4.0 cm electrode distance, the average removal efficiency (RE), efficiency capacity (EC) and energy consumption (Esp) were 57.99%, 20.18 g/(m3·h) and 190.2 (kW·h)/kg, respectively. The results of the RSM showed that the effects of the process parameters on the RE of MBC were as follows: current density > electrode distance > electrolyte concentration; the interactions effects on the RE of MBC were in the order of electrolyte concentration and current density > current density and electrode distance > electrolyte concentration and electrode distance; the optimal experimental conditions were as follows: the concentration of electrolyte was 0.149 mol/L, current density was 18.11 mA, electrode distance was 3.804 cm. Under these conditions, the RE achieved 66.43%. The response-surface variance analysis showed that the regression model reached a significant level, and the validation results were in agreement with the predicted results, which proved the feasibility of the model. The model can be applied to treat the CBS waste gas of polymer processes through electrochemical oxidation.