We apply new measurements of methanol, ethene, ethyne, and HCN from the Cross-track Infrared Sounder (CrIS) to explore the quantitative use of satellite-based thermal infrared (IR) observations for fire studies. We focus analysis on the western U.S. during the 2018–2019 timeframes of two fire-focused aircraft campaigns, and use the GEOS-Chem model to guide interpretation. The CrIS data reveal large in-smoke enhancements and species:species correlations for targeted volatile organic compounds (VOCs), especially during the more active 2018 fire year. Spectral enhancements are strongest for methanol and ethene. For VOCs with similar vertical sensitivities the in-smoke correlations are height-independent and can be converted to column enhancement ratios without plume altitude information. For VOCs with dissimilar vertical sensitivities, spectral index correlations change coherently with altitude and may constrain injection or plume height changes. The mean (± σ) ethene:methanol ratio measured by CrIS across an ensemble of plumes (0.64 ± 0.24 mol/mol) matches bottom-up emission ratios (0.63 ± 0.08 mol/mol), but satellite-based and aircraft data both reveal greater variability than is predicted by GEOS-Chem. We propose that fire pyrolysis conditions are one driver of this variability and  use in-situ data to show that near-field ethene:methanol ratios track pyrolysis conditions and hence inform the abundance of other emitted VOCs. Finally, we apply CrIS ethene:methanol ratios to estimate the high-temperature pyrolysis fraction for the same plume ensemble; the resulting fraction correlates with fire radiative power in a manner not well-captured by models.