The effects of various reaction conditions including temperature (200−240 °C), pressure (20−50 bar), and H₂/CO molar feed ratio (1−2) on the performance of the liquid-phase direct dimethyl ether (DME) synthesis from syngas, over a bifunctional catalyst (CuO/ZnO/Al₂O₃ + H-ZSM-5) have been studied. The experiments have been designed by general full factorial design (GFFD), and the effects of reaction conditions as well as their interactional effects on the yield of DME as the response variable have been determined. The investigation of the analysis of variation (ANOVA) table showed that all of the three variables and their interaction significantly affected the response. The relative order of importance of the factors on DME yield was found to be temperature > pressure > H₂/CO molar feed ratio. In addition, the optimum operating conditions for the maximum yield of DME were 240 °C, 50 bar, and H₂/CO = 2. Under these conditions, the yield of DME reached 51.0%.