We present top-down emission constraints for two non-CO2 greenhouse gases in large areas of the U.S. and southern Canada during early summer. Collocated airborne measurements of methane and nitrous oxide acquired during the COBRA-NA campaign in May–June 2003, analyzed using a receptor-oriented Lagrangian particle dispersion model, provide robust validation of independent bottom-up emission estimates from the EDGAR and GEIA inventories. We find that the EDGAR CH4 emission rates are slightly low by a factor of 1.08 ± 0.15 (2σ), while both EDGAR and GEIA N2O emissions are significantly too low, by factors of 2.62 ± 0.50 and 3.05 ± 0.61, respectively, for this region. Potential footprint bias may expand the statistically retrieved uncertainties. Seasonality of agricultural N2O emissions may help explain the discrepancy. Total anthropogenic U.S. and Canadian emissions would be 49 Tg CH4 and 4.3 Tg N2O annually, if these inventory scaling factors applied to all of North America.