Blockage in reservoirs caused by asphaltene deposits and inorganic interactions is a serious problem that may exacerbate the complexity of displacement characteristics in heterogeneous multilayer sandstone reservoirs and affect crude oil recovery performance during CO2 and CO2-WAG flooding. In this study, experiments of both CO2 and CO2-WAG flooding were carried out on the same multilayer systems under miscible conditions (70 degrees C, 18 MPa). The two flooding methods were evaluated for oil production performance and reservoir damage. The experimental results indicate that, after CO2 flooding, the entire system has a low oil recovery factor (RF) of 27.6%, and oil is produced mainly from the high permeability layer (91.4%), while the residual oil remains predominantly in the medium and low permeability layers. The injection pressure of CO2-WAG flooding is high, but the timing of CO2 breakthrough (BT) is late, and the oil RF of the entire system reaches 44.5%. The contribution rate of oil production in medium and low permeability layers is improved to 3.8% and 17.1%, respectively. Furthermore, the permeability of the high permeability layer decreases by 16.8% after CO2 flooding, which is mainly due to asphaltene precipitation. However, after CO2-WAG flooding, the permeability of each layer is significantly reduced, namely by 29.4%, 16.8%, and 6.9%, respectively. Asphaltene precipitation is still the main factor, but permeability decline caused by CO2 brine rock interactions cannot be ignored, especially in the high permeability layer (6.1%). Therefore, for multilayer reservoirs with high heterogeneity, CO2-WAG flooding provides the better oil displacement performance, but prevention and control measures for asphaltene precipitation are more necessary.