The effects of three key parameters of feed temperature, pressure, and flow rate were investigated on the catalytic reaction of methanol dehydration to dimethyl ether in a large-scale fixed bed. A one-dimensional mathematical model was employed for development of the optimum design and evaluation of temperature and concentration profiles. The study of the temperature profiles considering the catalyst behavior revealed that a maximum conversion is obtained under the feed temperature range of 523 to 533 K and operating pressures range of 1 to 1.5 Mpa. The inlet temperature was found to be the most major factor controlling the yield and rate of reaction. Also, the Rate-Conversion-Temperature chart was plotted to appraise and determine the optimal reactor volume at operating conditions.