Manufacturing industry is the foundation of building a country, the tool of rejuvenating the country and the foundation of strengthening the country. Enhancing the resilience of manufacturing industry is the key and focus of promoting the high-quality development of China’s manufacturing industry. Based on the panel data of A-share listed enterprises in Shanghai and Shenzhen stock exchanges from 2006 to 2020, combined with theoretical analysis and empirical test, this paper systematically studies the impact and mechanism of the establishment of free trade zone on the resilience of manufacturing enterprises. The research shows that the establishment of free trade zone has a positive impact on the resilience of manufacturing enterprises. The mechanism analysis shows that the agglomeration of innovation factors plays a mediating role in the impact of the establishment of free trade zones on the resilience of manufacturing enterprises, and its indirect effect accounts for 962% of the total effect. Digital transformation, three different types of industrial agglomeration and the synergistic effect of the establishment of free trade zones all strengthen the promotion effect of the establishment of free trade zones on the resilience of manufacturing enterprises to varying degrees. Heterogeneity analysis shows that for the eastern region, the establishment of free trade zone has a significant positive impact on the resilience of manufacturing enterprises. With the increase of the distance to the free trade zone, the driving effect of the free trade zone on the resilience of manufacturing enterprises in surrounding cities will show a wave-like convergence trend of “increasing first, then decreasing, then increasing and decreasing, and finally approaching 0”. For the start-up manufacturing enterprises, the establishment of the free trade zone has a significant effect on improving their resilience level.