CONTEXT: Minimizing nitrogen (N) surplus in croplands is a key objective of sustainable agricultural intensification and is crucial for climate change mitigation and adaptation strategies. Previous studies often focus on the cultivation of staple crops and lack integration between exploring the driving mechanisms of crop N uptake and adjusting cropping structures. OBJECTIVE: This study focused on spatially explicit quantification and modelling of N flows and N use efficiency (NUE) of eight major crops (rice, maize, wheat, soybean, peanut, oilseed rape, cotton, and potato) from 2004 to 2020 at the regional scale in China. This study further provided strategies to reduce N surplus while ensuring food security and farming profit. METHODS: Structural equation models and random forest models were used to analyse the multiple effects of natural and socio-economic factors and farming inputs on crop N uptake. Optimization models were applied to simulate the potential to reduce N surplus by optimizing N fertilization and adjusting the cropping structure under multiple scenarios, considering cropping calendars, maintaining stable farming profit, and limiting irrigation water use. RESULTS AND CONCLUSIONS: The NUE of the eight major crops increased from 2004 to 2020. However, high yield per unit area did not always translate into high total production, reflecting constraints from sown area allocation, unrealized yield potential, and N surplus risk. Increased mechanization, reduced land fragmentation, appropriate N fertilization and irrigation increased crop N uptake, while excessive pesticide use and adverse soil or climatic conditions could limit it. The effects of farming inputs on crop N uptake usually reached saturation. For instance, the effects of N fertilization were saturated at 200 kg N ha-1 yr-1 and 70 kg N ha-1 yr-1 for wheat and soybean, respectively. Under various optimization scenarios, the N surplus decreased by 9.2-19%, and the overall NUE increased by 2.3-6.2%. Nationwide coordination of crop profits through transfer payments and optimizing N fertilization increased the NUE and reduced N surplus, resulting in approximately twice as many benefits. Adjustments to cropping structure could also reduce irrigation water use by 5.8-9.3%, especially in northern arid and semiarid regions. SIGNIFICANCE: This study provides region-specific recommendations to optimize farming inputs and cropping structures, aiming to reduce environmental N losses while maintaining food security and farmer income.