We present estimates of regional methane (CH4) emissions from oil and natural gas operations in the Barnett Shale, Texas, using airborne atmospheric measurements. Using a mass balance approach on eight different flight days in March and October 2013, the total CH4 emissions for the region are estimated to be 76 ± 13 × 103 kg hr−1 (equivalent to 0.66 ± 0.11 Tg CH4 yr−1; 95% confidence interval (CI)). We estimate that 60 ± 11 × 103 kg CH4 hr−1 (95% CI) are emitted by natural gas and oil operations, including production, processing, and distribution in the urban areas of Dallas and Fort Worth. This estimate agrees with the U.S. Environmental Protection Agency (EPA) estimate for nationwide CH4 emissions from the natural gas sector when scaled by natural gas production, but it is higher than emissions reported by the EDGAR inventory or by industry to EPA’s Greenhouse Gas Reporting Program. This study is the first to show consistency between mass balance results on so many different days and in two different seasons, enabling better quantification of the related uncertainty. The Barnett is one of the largest production basins in the United States, with 8% of total U.S. natural gas production, and thus, our results represent a crucial step toward determining the greenhouse gas footprint of U.S. onshore natural gas production.