The pyrolysis characteristics of oil shale during heat treatment dominate the oil production of kerogen. In this study, the pyrolysis characteristics of oil shale in a laboratory microwave apparatus were investigated based on a novel fully coupled three-dimensional electromagnetic-thermal-chemical-hydraulic model according to the experimental microwave apparatus. By simulating the electric field, temperature distribution, and kerogen decomposition within oil shale subjected to microwave irradiation, several parameters, including waveguide, position, and power, were successfully optimized. The results indicated that the non-uniform temperature distribution was consistent with the distribution of the electric field. Double microwave ports were more effective than single ports in terms of heating rate and temperature uniformity. There was an optimal location where the highest heating efficiency was obtained, which was on the left of the cavity center. When irradiation was conducted over a range of microwave powers, a higher power was suitable for achieving a rapid temperature increase, whereas a lower power was suitable to gain a high efficiency of the pyrolysis rate. Therefore, a variable power heating mode was introduced to decrease the heating time and improve the heat uniformity simultaneously during oil shale pyrolysis. Specifically, the secondary reactions of oil products should be maximally avoided by controlling the microwave power.