Methane is a powerful greenhouse gas, and a primary target for mitigating climate change in the short-term future due to its relatively short atmospheric lifetime and greater ability to trap heat in Earth’s atmosphere compared to carbon dioxide. Top-down observations of atmospheric methane are possible via drone and aircraft surveys as well as satellites such as the TROPOspheric Monitoring Instrument (TROPOMI). Recent work has begun to apply the divergence method to produce regional methane emission rate estimates. Here we show that when the divergence method is applied to spatially incomplete observations of methane, it can result in negatively biased time-averaged regional emission rates. We show that this effect can be counteracted by adopting a procedure in which daily advective fluxes of methane are time-averaged before the divergence method is applied. Using such a procedure with TROPOMI methane observations, we calculate yearly Permian emission rates of 3.1, 2.4 and 2.7 million tones per year for the years 2019 through 2021. We also show that highly-resolved plumes of methane can have negatively biased estimated emission rates by the divergence method due to the presence of turbulent diffusion in the plume, but this is unlikely to affect regional methane emission budgets constructed from TROPOMI observations of methane. The results from this work are expected to provide useful guidance for future implementations of the divergence method for emission rate estimation from satellite data—be it for methane or other gaseous species in the atmosphere.