Nitrous oxide (N2O) is an important gas for climate and for stratospheric chemistry, with a lifetime exceeding 100 years. Global concentrations have increased steadily since the 18th century, apparently due to human-associated emissions, principally from the application of nitrogen fertilizers. However, quantitative studies of agricultural emissions at large spatial scales are lacking, inhibited by the difficulty of measuring small enhancements in atmospheric concentration. Here we derive regional emission rates for N2O in the agricultural heartland of California based on analysis of in-situ airborne atmospheric observations collected using a new quantum cascade laser spectrometer. The data were obtained on board the NOAA WP-3 research aircraft during the CalNex (California Research at the Nexus of Air Quality and Climate Change) program in late spring 2010. We coupled the WRF (weather research and forecasting) model, a meso-scale meteorology model, with the STILT (stochastic time-inverted Lagrangian transport) model, a Lagrangian particle dispersion model, to link our in-situ airborne observations to surface emissions. We then used a variety of statistical methods to identify source areas and to optimize emission rates. Our results are consistent with the view that fertilizer application is the largest source of N2O in the Central Valley. The spatial distribution of surface emissions, based on California land use and activity maps, was very different than indicated in the leading emission inventory (EDGAR 4.0). Our estimated total emission flux of N2O for California in May and June was 3 – 4 times larger than the annual mean given for the state by EDGAR and other inventories, indicating a strong seasonal variation. We estimated the statewide total annual emissions of N2O to be 0.042 ± 0.011 Tg N/year, roughly equivalent to inventory values if we account for seasonal variations using observations obtained in the midwestern United States. This state total N2O emission is 20.5 Tg CO2 equivalent (100 year global warming potential = 310 CO2 eq/g N2O), accounting for approximately 4% of the state total greenhouse gas emissions.