In this study, the process parameters used for the synthesis of sulfonated polyketone in the preparation of ion exchange membranes were optimized using the response surface methodology (RSM). Sulfonated polyketone ion exchange membranes were prepared by varying three process parameters: concentration of the sulfonating agent, reaction temperature, and reaction time. The properties of the prepared membranes, such as the degree of sulfonation, water uptake, swelling ratio, ion exchange capacity, and mechanical properties, were evaluated. According to the RSM analysis, the degree of sulfonation and swelling ratio of the sulfonated polyketone ion exchange membranes were predominantly affected by the concentration of the sulfonating agent, whereas the water uptake and mechanical properties were predominantly affected by the reaction temperature. The optimal process parameters determined for the synthesis of sulfonated polyketone in the ion exchange membranes are: sulfonating agent concentration of 0.4 wt.%, reaction temperature of 40°C, and reaction time of 62.6 min, which resulted in an ion exchange capacity of 0.88 meq/g. Based on these results, it was concluded that the analysis using RSM is very useful because the experiments and statistical analysis showed similar results.