Abstract Enhancement ratios among trace gases co-emitted by combustion of fossil fuels vary with emission sources and their combustion efficiency. We used column-averaged dry-air mole fractions of carbon dioxide (XCO2), methane (XCH4), and carbon monoxide (XCO) from the Greenhouse gases Observing SATellite-2 (GOSAT-2), a unique satellite that observes them simultaneously with the same field of view, to derive the enhancement ratios (ΔXCO/ΔXCO2, ΔXCO/ΔXCH4, and ΔXCH4/ΔXCO2) for the 40 most populous cities in the world. These enhancement ratios were used to evaluate the Emissions Database for Global Atmospheric Research (EDGAR). For cities where the difference in the 2015 EDGAR CO emissions between the latest versions (v6.1 and v5.0) was 30% or less, the GOSAT-2 ΔXCO/ΔXCO2 ratios and EDGAR (v6.1/v7.0) CO/CO2 emission ratios were in good agreement (correlation coefficient of 0.65). For ~70% of the cities where the difference of CO emissions exceeded 30%, the EDGAR CO/CO2 emission ratios using v6.1 CO emissions were in better agreement with the GOSAT-2 ΔXCO/ΔXCO2 ratios than those using v5.0 CO emissions, indicating that v6.1 CO emissions were improved over v5.0 emissions. However, for the remaining cities, the version upgrade may have reduced the CO emissions too much. The CH4 and CO emissions for each city were then estimated from the ΔXCH4/ΔXCO2 and ΔXCO/ΔXCO2 ratios, respectively, by reference to the CO2 emissions from the Open-data Inventory for Anthropogenic CO2 (ODIAC) or EDGAR. Compared to our estimates using the ODIAC (EDGAR) CO2 emissions, the EDGAR v7.0 CH4 and v6.1 CO emissions were underestimated for 74% (57%) and 76% (53%), respectively, of all cities where results were available. For several cities where emissions were estimated using in situ observations and ground-based remote sensing observations, our results were in reasonable agreement with these results. The implication is that satellite-derived enhancement ratios can provide informative constraints on anthropogenic emissions in megacities.