The overuse of Nitrogen (N) fertilizers on smallholder farms in rapidly developing countries has increased greenhouse gas (GHG) emissions and accelerated global N consumption over the past 20 years. In this study, a regional N management approach was developed based on the cost of the agricultural response to N application rates from 1,726 on-farm experiments to optimize N management across 12 agroecological subregions in the intensive Chinese smallholder maize belt. The grain yield and GHG emission intensity of this regional N management approach was investigated and compared to field-specific N management and farmers' practices. The regional N rate ranged from 150 to 219 kg N ha(-1) for the 12 agroecological subregions. Grain yields and GHG emission intensities were consistent with this regional N management approach compared to field-specific N management, which indicated that this regional N rate was close to the economically optimal N application. This regional N management approach, if widely adopted in China, could reduce N fertilizer use by more than 1.4 MT per year, increase maize production by 31.9 MT annually, and reduce annual GHG emissions by 18.6 MT. This regional N management approach can minimize net N losses and reduce GHG emission intensity from over- and underapplications, and therefore can also be used as a reference point for regional agricultural extension employees where soil and/or plant N monitoring is lacking.