Few studies have investigated how the reclamation of the desert to cropland affects soil nitrous oxide (N2O) emissions. A study site was initiated in 2005 at the southern Taklimakan Desert by establishing four fields along the desert−oasis ecotone. Three fields were reclaimed as croplands for continuous cotton (Gossypium hirsutum L.) production and received (1) high, (2) low, and (3) no fertilizer inputs and the fourth field remained as a native desert. Static-chamber monitoring of N2O flux was conducted from April 2019 to March 2021. N2O emissions occurred in cropland mainly after drip fertigation during the growing season. The two−year N2O emissions in the desert, no fertilizer, low fertilizer, and high fertilizer were 248, 670, 2232, and 3615 g N ha−1, respectively. The native desert was a weak source of N2O emissions, with the non−growing season emissions accounting for 66% of the annual emissions. N2O emissions from farmland mainly occurred over the growing season, accounting for 73−98% of the total annual emissions. The N2O flux was positively related to soil NO3−−N concentration and soil water−filled pore space (WFPS), highlighting the importance of soil N availability and moisture in affecting N2O emissions in extremely arid areas. Our results demonstrate that land reclamation from the desert to cropland significantly increased N2O emissions due to high nutrient inputs. Thus, appropriate fertilizer management in the reclaimed land is essential for maintaining yield, improving soil quality, and reducing N2O emissions for continuous cotton production.