CO2 injection to enhance coalbed methane (CO2-ECBM) production is a promising technology for realizing the efficient exploitation of new energy resource, but its effect is cooperatively affected by miscellaneous influencing factors. To elucidate the mechanism and increase the efficiency of the displacement of CH4 by CO2, CO2 flooding experiments under the influence of the injection pressure, confining pressure, and temperature were conducted. The results show that an increase in the injection pressure enlarges the pore-fracture network of the coal matrix and promotes its gas adsorption ability and seepage capacity, while an increase in the confining pressure compresses the coal body and reduces the adsorption capacity and permeability. Increasing the temperature enhances kinetic energy and induces the thermal swelling effect, which disfavors the adsorption and seepage processes. The CO2 adsorption capacity is larger than the CH4 adsorption capacity due to the higher adsorption affinity of CO2, but the CO2 permeability is lower than the CH4 permeability due to the severe adsorption swelling effect. The CO2 flooding process is characterized by three parameters (equal percentage displacement time, displacement rate, and displacement efficiency) and can be divided into the CO2 driving stage, replacement and displacement stage, and equilibrium stage. The injection pressure and temperature decrease the displacement time and increase the displacement rate and displacement efficiency, while confining pressure shows the opposite trends. Multifactor interaction models of the displacement efficiency of coal seams at various buried depths were established and demonstrated to appropriately predict the displacement efficiency of CO2-ECBM in deep coal seams. The displacement efficiency is controlled by the reservoir performance, geological characteristics, and CO2 injection technology. The selection of a high-permeability coal reservoir and coal seams with an appropriate buried depth and the development of a reasonable injection plan are suggested for the implementation of CO2-ECBM extraction.