Nitrous oxide (N₂O), a potent greenhouse gas and ozone depleting substance, plays a crucial role in the atmosphere. Anthropogenic emissions from agriculture contribute to a rising trend in global N₂O emissions and atmospheric concentrations. However, due to insufficient direct observations, regional N₂O emissions derived in bottom-up and top-down studies are highly uncertain. The U.S. Midwest is one of the most intensive agriculture areas worldwide and hence may contribute significantly to the observed trend. Recent top-down studies suggest that bottom-up estimates underestimate agricultural emissions in that area by up to an order of magnitude. Here we quantify nitrous oxide emissions in the Midwest in October 2017 and June-July 2019 with a top-down approach. Unique continuous aircraft-based measurements of N₂O conducted during the ACT-America campaign together with forward WRF-Chem model simulations are used to scale the EDGAR inventory thus quantifying emissions. On average we had to upscale October 2017 and June-July 2019 agricultural EDGAR 4.3.2/5.0 emissions by a factor of 6.3/3.5 and 11.4/9.9, resulting in 0.42 nmol m^-2 s^-1 and 1.06 nmol m^-2 s^-1 emissions in the Midwest, respectively. Finally, calculations of direct soil N₂O emissions from the DayCent biogeochemical model are compared to our estimates.