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℃, 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%), whilst 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.