Limiting emissions of climate-warming methane from oil and gas (O&G) is a major opportunity for short-term climate benefits. We deploy a basin-wide airborne survey of O&G extraction and transportation activities in the New Mexico Permian Basin, spanning 35 923 km2, 26 292 active wells, and over 15 000 km of natural gas pipelines using an independently validated hyperspectral methane point source detection and quantification system. The airborne survey repeatedly visited over 90% of the active wells in the survey region throughout October 2018 to January 2020, totaling approximately 98 000 well site visits. We estimate total O&G methane emissions in this area at 194 (+72/–68, 95% CI) metric tonnes per hour (t/h), or 9.4% (+3.5%/–3.3%) of gross gas production. 50% of observed emissions come from large emission sources with persistence-averaged emission rates over 308 kg/h. The fact that a large sample size is required to characterize the heavy tail of the distribution emphasizes the importance of capturing low-probability, high-consequence events through basin-wide surveys when estimating regional O&G methane emissions.