Depressurization combined with thermal stimulation is a promising method for gas hydrate production. Owing to its advantages of rapid uniform heating, microwave radiation is an efficient source of heat. However, the mechanisms of hydrate decomposition under depressurization combined microwave stimulation are currently unclear. In this study, methane hydrate was synthesized under 6 MPa and 2 °C, with hydrate saturation of approximately 42% in natural quartz sand. We then compared hydrate decomposition via rapid depressurization and piecewise depressurization, with or without microwave stimulation at 2.45 GHz and 400 W. When using the depressurization method alone, the hydrate decomposition rate increased with the depressurization amplitude. However, in the last stage of hydrate decomposition, the external flow of gas was hindered by the Jamin effect, especially under larger depressurization amplitudes; therefore, extremely low production pressure is not justified. When combined with microwave stimulation, both depressurization methods resulted in increased reservoir temperature within a few seconds, and microwave heating provided an extra driving force for hydrate decomposition. Furthermore, microwave heating was more effective when larger amounts of undecomposed hydrate remained after depressurization. When depressurization was combined with microwave stimulation, the average gas production rate at 100% gas production was 0.269−0.601 L/min, which was significantly higher than that for depressurization alone. However, the energy efficiency ratio was approximately 1, which has no practical value. Conversely, the average gas production rate at 90% gas production was 0.452−2.945 L/min and the energy efficiency ratio was 2.9−17.6. Under the combined method, gas hydrate decomposition at a production pressure of 1.9 MPa achieved the subtle balance between the average gas generation rate and energy efficiency. Thus, optimizing the gas production pressure and microwave stimulation time can improve the average gas production rate and energy efficiency ratio according to the reservoir hydrate conditions.