Abstract Accurate regional methane (CH4) emission monitoring is essential for effective climate mitigation but remains constrained by limited observational networks and challenged by diffuse emission sources. Here, we present an innovative regional CH4 inversion system integrating satellite-based carbon monoxide (CO) observations with ground-based CH4-to-CO flux ratios. Our study estimates China’s CH4 fluxes between 2000 and 2021, revealing an average of 48.4 ± 13.8 Tg yr−1 and a significant increasing trend of 1.1 ± 0.2 Tg yr−2. Over the 22-year period, socio-economic development drove a 92.1 Tg increase in China’s CH4 fluxes, partially offset by a 78.1 Tg reduction due to declining emission intensity; however, this mitigating effect weakened after 2015. Our results demonstrate comparability with independent estimates, and comprehensive sensitivity and uncertainty analyses confirm the robustness of our approach. This study highlights the potential of integrating air pollution monitoring into tracking regional greenhouse gas emissions.