Arable soils are a large source of nitrous oxide (N2O) emissions, making up half of the biogenic emissions worldwide. Estimating their source strength requires methods capable of capturing the spatial and temporal variability of N2O emissions, along with the effects of crop management. Here we applied a process-based model, Crop Environmental REsources Synthesis (CERES), with geo-referenced input data on soils, weather, and land use to map N2O emissions from wheat-cropped soils in three agriculturally intensive regions in France. Emissions were mostly controlled by soil type and local climate conditions, and only to a minor extent by the doses of fertilizer nitrogen applied. As a result, the direct emission factors calculated at the regional level were much smaller (ranging from 0.0007 to 0.0033 kg N2O-N kg-1 N) than the value of 0.0125 kg N2O-N kg-1 N currently recommended in the IPCC Tier 1 methodology. Regional emissions were far more sensitive to the soil microbial characteristics governing denitrification and its fraction evolved as N2O, soil bulk density, and soil initial inorganic N content. Mitigation measures should therefore target a reduction in the amount of soil inorganic N upon sowing of winter crops, and a decrease of the soil N2O production potential itself. From a general perspective, taking into account the spatial variability of soils and climate thereby appears necessary to improve the accuracy of national inventories, and to tailor mitigation strategies to regional characteristics.