<p>Driven by the dual dynamics of global industrial chain restructuring and high-quality domestic economic development, enhancing the resilience of industrial chains has become a crucial goal for the transformation and upgrading of China’s manufacturing industry. As an innovative policy tool proposed in recent years, the “Chain Chief System” aims to strengthen industrial security and risk resistance capabilities by building cross-departmental collaborative networks. However, existing research has not yet systematically evaluated the actual effects and mechanisms of this policy on the resilience of the manufacturing industrial chain. Based on provincial input-output data from 2015 to 2022, this paper treats the Chain Chief System as a quasi-natural experiment and uses a progressive dual difference model to empirically analyze its impact on the resilience of the manufacturing industrial chain. Empirical results show that the implementation of the Chain Chief System has significantly improved the level of regional manufacturing industrial chain resilience. Moreover, this effect exhibits significant heterogeneity in the eastern coastal areas and technology-intensive industries, highlighting the structural matching relationship between policy implementation and regional development foundations and industrial characteristics. Further mechanism tests reveal that industrial collaborative innovation, optimization of the business environment, and improvement of resource allocation efficiency constitute the key pathways through which the policy exerts its effects. The research results provide policy insights for enhancing the resilience of the manufacturing industrial chain in complex economic environments.</p>