Chloromethanes, including mono, di, tri, and tetrachloromethane, can contribute to stratospheric ozone depletion and hinder ozone layer recovery. Leakage from industrial chloromethane production plants is a major anthropogenic source of chloromethanes; however, accurate estimations of the emission factors are limited. In this study, a plant-scale inversion system was established using field measurements, dispersion simulation, and inversion algorithms to quantify the emission factors of chloromethanes from chloromethane production plants. The results show that, with the exception of the emission factors (kg/kg respective chloromethane produced) of trichloromethane (0.02 ± 0.006), those of dichloromethane (0.04 ± 0.02) and tetrachloromethane (0.03 ± 0.02) were comparable to those provided by the Intergovernmental Panel on Climate Change (0.04 kg/kg fluorinated gas produced). Compared with previous records of emission factors of chloromethanes, this study provided the latest and, to the best of our knowledge, the first field-measurement based estimates of emission factors. Subsequently, using these latest estimates, the emissions of monochloromethane (56 ± 21 Gg/yr), dichloromethane (43 ± 18 Gg/yr), trichloromethane (9.6 ± 3.9 Gg/yr), and tetrachloromethane (2.2 ± 1.6 Gg/yr) from chloromethane production plants in China from 2020 were estimated. Considering the detrimental effects of chloromethanes for ozone layer recovery, the method developed in this study can provide valuable insights for studying emission factors of chloromethanes from other sources and other ozone-depleting substances to accurately assess their impact on the ozone layer.