This paper presents top-down constraints on the magnitude, spatial distribution, and seasonality of nitrous oxide (N2O) emissions over the central United States. We analyze data from tall towers in 2004 and 2008 using a high resolution Lagrangian particle dispersion model paired with both geostatistical and Bayesian inversions. Our results indicate peak N2O emissions in June with a strong seasonal cycle. The spatial distribution of sources closely mirrors data on fertilizer application with particularly large N2O sources over the US Cornbelt. Existing inventories for N2O predict emissions that differ substantially from the inverse model results in both seasonal cycle and magnitude. We estimate a total annual N2O budget over the central US of 0.9–1.2 TgN/yr and an extrapolated budget for the entire US and Canada of 2.1–2.6 TgN/yr. By this estimate, the US and Canada account for 12–15% of the total global N2O source or 32–39% of the global anthropogenic source as reported by the Intergovernmental Panel on Climate Change in 2007.