Mesoporous sulfur-doped graphitic carbon nitride (MCNS) materials were successfully synthesized using thiourea as a low-cost precursor and SiO2 gel solution as a template through a simple thermal condensation method. The effects of three synthesis key factors, namely, the reaction temperature, the reaction time, and the weight ratio of SiO2/thiourea, and also their interactions on the removal rate of methyl orange (MO) were investigated using response surface methodology, and the samples were subjected to several characterization techniques. Results showed that the optimized physicochemical properties could be achieved for the MCNS samples by controlling the synthesis key factors, and it was found that the reaction temperature and the reaction time had significant influences on the MO photocatalytic removal. Among bulk graphitic carbon nitride (g-C3N4), CN (undoped g-C3N4), CNS (sulfur-doped g-C3N4 without template), and TiO2 (Degussa P25) samples, the optimized MCNS-4 illustrated the highest photocatalytic activity toward the removal of MO under visible light irradiation. The enhanced performance originated from the synergistic effects of high surface area, mesoporous texture, sulfur doping, and high visible light absorption, which were helpful for the separation and transportation of the photogenerated electron hole pairs. Furthermore, MCNS-4 revealed high reusability and stability-without any significant decrease in its efficiency. Our findings not only confirm the importance of simultaneous sulfur doping and mesoporous structure to synthesize highly active photocatalysts but also might provide a new insight into textural engineering of carbon nitride materials only by the optimization of the synthesis key variables, considering their interactions without relying on extra metal oxides.