Abstract: As the core guarantee regions of China’s national food security strategy, the major grain-producing areas play a crucial role in ensuring national food security resilience. Understanding the spatiotemporal dynamics and driving mechanisms of food security resilience in these regions is vital for achieving the goals of building a strong agricultural sector and promoting sustainable rural development. Based on statistical data from China’s major grain-producing areas from 2000 to 2020, we constructed a food security resilience evaluation index system that encompasses the resilience of the industry, supply, and value chains, grounded in resistance, adaptability, and transformation capacity. Specifically, the entropy method was employed to quantify the resilience levels of the industrial, supply, and value chains (three-chain) in food security, whereas a coupling coordination model was applied to measure their synergy. Kernel density estimation was used to examine the absolute differences and variation characteristics. Furthermore, the contributions of the subsystem indicators were ranked using the random forest algorithm, identifying nine key factors with significant importance, and the geographical detector method was employed to interpret their driving effects on food security resilience. From 2000 to 2020, the resilience levels of the grain industrial, supply, and value chains in the major grain-producing areas increased by 0.180, 0.253, and 0.141, respectively. Jiangsu Province showed the highest growth rate for three chains resilience. During the same period, the degree of coupled coordination of food security resilience increased from 0.371 to 0.571, indicating a shift from mild imbalance to fragile coordination. Shandong and Jiangsu Provinces exhibited relatively high coupling coordination, reaching intermediate coordination levels, whereas Inner Mongolia, Jilin, and Liaoning remained near imbalances. The overall coordination level of the three chains in food security resilience continuously improved, with substantial inter-provincial disparities in the early study period, gradually narrowing over time and trending toward equilibrium, but without a universal convergence trend. Among the subsystems, the value chain resilience factors had a greater driving effect on the coordination of the three chains than the supply and industrial chain resilience factors. At the individual factor level, the gross output value of agriculture, forestry, animal husbandry, and fishery, as well as the general public budget revenue, were identified as the key influencing factors for the coordination of the three chains, which were also affected by multi-factor interactions. These findings provide decision-making references for enhancing food security resilience in major grain-producing areas and contribute to establishing a new food security framework characterized by deep coordination among the “three-chain” in China’s major grain-producing areas.