Natural gas production in the U.S. has increased rapidly over the past decade, along with concerns about methane (CH
4
) leakage (total fugitive emissions), and climate impacts. Quantification of CH
4
emissions from oil and natural gas (O&NG) operations is important for establishing scientifically sound, cost‐effective policies for mitigating greenhouse gases. We use aircraft measurements and a mass balance approach for three flight experiments in August and September 2015 to estimate CH
4
emissions from O&NG operations in the southwestern Marcellus Shale region. We estimate the mean ± 1
σ
CH
4
emission rate as 36.7 ± 1.9 kg CH
4
s
−1
(or 1.16 ± 0.06 Tg CH
4
yr
−1
) with 59% coming from O&NG operations. We estimate the mean ± 1
σ
CH
4
leak rate from O&NG operations as 3.9 ± 0.4% with a lower limit of 1.5% and an upper limit of 6.3%. This leak rate is broadly consistent with the results from several recent top‐down studies but higher than the results from a few other observational studies as well as in the U.S. Environmental Protection Agency CH
4
emission inventory. However, a substantial source of CH
4
was found to contain little ethane (C
2
H
6
), possibly due to coalbed CH
4
emitted either directly from coalmines or from wells drilled through coalbed layers. Although recent regulations requiring capture of gas from the completion venting step of the hydraulic fracturing appear to have reduced losses, our study suggests that for a 20 year time scale, energy derived from the combustion of natural gas extracted from this region will require further controls before it can exert a net climate benefit compared to coal.