The use of satellite instruments to detect and quantify methane emissions from fossil fuel production activities is highly beneficial to support climate change mitigation. Different hyperspectral and multispectral satellite sensors have recently shown potential to detect and quantify point-source emissions from space. The Sentinel-2 (S2) mission, despite its limited spectral design, supports the detection of large emissions with global coverage and high revisit frequency thanks to coarse spectral coverage of methane absorption lines in the shortwave infrared. Validation of S2 methane retrieval algorithms is instrumental in accelerating the development of a systematic and global monitoring system for methane point sources. Here, we develop a benchmarking framework for such validation. We first develop a methodology to generate simulated S2 datasets including methane point-source plumes. These benchmark datasets have been created for scenes in three oil and gas basins (Hassi Messaoud, Algeria; Korpeje, Turkmenistan; Permian Basin, USA) under different scene heterogeneity conditions and for simulated methane plumes with different spatial distributions. We use the simulated methane plumes to validate the retrieval for different flux rate levels and define a minimum detection threshold for each case study. The results suggest that for homogeneous and temporally invariant surfaces, the detection limit of the proposed S2 methane retrieval ranges from 1000 to 2000 kg h−1, whereas for areas with large surface heterogeneity and temporal variations, the retrieval can only detect plumes in excess of 500 kg h−1. The different sources of uncertainty in the flux rate estimates have also been examined. Dominant quantification errors are either wind-related or plume mask-related, depending on the surface type. Uncertainty in wind speed, both in the 10 m wind (U10) and in mapping U10 to the effective wind (Ueff) driving plume transport, is the dominant source of error for quantifying individual plumes in homogeneous scenes. For heterogeneous and temporally variant scenes, the surface structure underlying the methane plume affects the plume masking and can become a dominant source of uncertainty.