Air pollution emissions from ports are major sources of contaminant exposures to downwind communities. Elevated pollutant concentrations relate to emissions from port activities and nearby heavy industries including refining. Methane (CH4) in the 66 Refinery plume, located west of the Los Angeles Port, provided a real-world validation opportunity for in situ-derived emissions in comparison with imaging spectroscopy-derived emissions.Airborne remote sensing data were acquired by the airborne thermal infrared Mako imaging spectrometer, while contemporaneous in situ meteorology and trace gas measurements and air samples were collected using a ground based mobile system, SISTER™ (Standard Instrumentation Suite: Truck Enabled for Response). SISTER measures 13 trace gases, meteorology, aerosol size distributions, and vertical aerosol profiles at up to highway speeds. Real-time data visualization is used to target sample collection. SISTER & Mako data were collected 19 June 2020 with additional SISTER data including air samples collected 16 July 2020.In situ CH4 emissions were derived from two series of inversion plume models with different numbers of plumes for comparison with Mako reference emissions. The informed series used Mako spatial data, whereas the uninformed series did not. In situ survey data and air samples also were collected for two nearby oil wells and found significantly elevated alkanes through undecane and aromatics in the refinery and oil well plumes compared to nearby reference air.Remote sensing CH4 emissions were 69 g s−1 (2.18 Gg yr−1), within 20% of the informed in situ emissions of 87 g s−1 (2.73 Gg yr−1) and within 10% of four-plume uninformed emissions of 80 g s−1 (2.51 Gg yr−1). On an annualized basis, this is 10% of estimated US refining CH4 emissions. Derived emissions were robust – agreeing within 10–20% for the various models; however, partitioning between plumes was very poor for the uninformed plumes because neglecting wind veering caused emissions mis-assignment. Monte Carlo simulation emission uncertainties were 12–13% for 19 June and 24–25% for 16 July when emissions were much lower, 0.25 Gg CH4 yr−1.This study emphasized the importance of fine-scale structure in winds with respect to characterizing emissions at the sub-facility (kilometer) scale, while also showing robust estimation of emissions at the facility scale by in situ survey for a wide range of models. Wind structure on kilometer and smaller scales plays a key role in understanding the fate of emissions.