The study of anthropogenic carbon monoxide (CO) emissions is crucial to investigate anthropogenic activities. Assuming the anthropogenic CO emissions accounted for the super majority of the winter CO fluxes in western Europe, they could be roughly estimated by the inversion approach. The CO fluxes and concentrations of four consecutive winter seasons (i.e., December–February) in western Europe since 2017 were estimated by a regional CO flux inversion system based on the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) and the Data Assimilation Research Testbed (DART). The CO retrievals from the Measurements Of Pollution In The Troposphere instrument (MOPITT) version 8 level 2 multi-spectral Thermal InfraRed (TIR)/Near-InfraRed (NIR) CO retrieval data products were assimilated by the inversion system. The analyses of the MOPITT data used by the inversion system indicated that the mean averaging kernel row sums of the surface level was about 0.25, and the difference percentage of the surface-level retrievals relative to a priori CO-mixing ratios was 14.79%, which was similar to that of the other levels. These results suggested the MOPITT’s surface-level observations contained roughly the same amount of information as the other levels. The inverted CO fluxes of the four winter seasons were 6198.15 kilotons, 4939.72 kilotons, 4697.80 kilotons, and 5456.19 kilotons, respectively. Based on the assumption, the United Nations Framework Convention on Climate Change (UNFCCC) inventories were used to evaluate the accuracy of the inverted CO fluxes. The evaluation results indicated that the differences between the inverted CO fluxes and UNFCCC inventories of the three winter seasons of 2017–2019 were 13.36%, −4.59%, and −4.76%, respectively. Detailed surface-CO concentrations and XCO comparative analyses between the experimental results and the external Community Atmosphere Model with Chemistry (CAM-Chem) results and the MOPITT data were conducted. The comparative analysis results indicated that the experimental results of the winter season of 2017 were obviously affected by high boundary conditions. The CO concentrations results of the experiments were also evaluated by the CO observation data from Integrated Carbon Observation System (ICOS), the average Mean Bias Error (MBE), and the Root Mean Square Error (RMSE) between the CO concentrations results of the inversion system, and the ICOS observations were −22.43 ppb and 57.59 ppb, respectively. The MBE and RMSE of the inversion system were 17.53-ppb and 4.17-ppb better than those of the simulation-only parallel experiments, respectively.