Considering the limitations of a single method for hydrate recovery, the combination of the traditional methods receives more attention nowadays. In this work, the gas production behavior from a synthesized methane hydrate reservoir by the combined method of ethylene glycol (EG) injection and depressurization was investigated in a medium-size three-dimensional reactor. The hydrate-bearing sediments were prepared according to the temperature and pressure conditions of the South China Sea reservoir. The results indicated that the production period could be significantly shortened by the combination method. After comparison of different EG injection conditions, it is found that the migration characteristics of EG solution in the reservoir were quite different in the EG injection stage, which caused different gas production rates in the follow-up process. Moreover, the increase of the EG concentration or EG injection volume could enhance the gas production rate. From analysis of the evolution of the low-temperature region, it is seen that EG was mainly concentrated between the injection well and production well. The migration of EG was largely influenced by the injection rate. When a higher EG injection rate was used, EG solution would arrive at the production well faster and spread to a larger region over time. It is necessary to avoid EG output caused by excessive injection. In addition, EG efficiency was found to be influenced by EG injection patterns. The maximum values of EG efficiency could be enhanced significantly by decreasing the EG concentration. Meanwhile, the EG efficiency at the end of gas production also relied on the injection volume and injection rate.