Although importance of high-yielding maize system for food security has been extensively studied and discussed worldwide, more must be done in the context of improving yield while simultaneously reducing agricultural environmental costs to achieve sustainable intensification (SI). Using China's maize production as an example, we discussed the system with equal emphasis on high yield and high nitrogen (N) use efficiency in regards to SI. Through yield potentials and gaps analysis with the help of crop modeling, the high-yielding maize system was designed and developed to make maximum use of solar energy and growing season with favorable temperatures via genetics × environment × management (G × E × M) interactions. In this high-yielding system compared with the low-yielding traditional farmers system, total dry matter increased with stable harvest index, aboveground plant N uptake requirement per grain yield deceased largely, and the percentage of the dry matter and N accumulation during the middle-late growing season increased significantly. Accordingly, an in-season root-zone N management was developed for high-yielding maize system to match the total N requirement by crop in application amount, placement, and timing for nonlimiting N supply with minimum losses to the environment. The high-yielding system showed great potential for SI which reduced N2O and other greenhouse gas emission intensity by 10%–30%. Moreover, we suggest future research direction for high-yielding maize system to address multiply challenges in a changing world including climate change, resource depletion and shortage, and soil constrains and degradation to ensure food security.