The digitalization process of China's manufacturing industry has entered a critical period, and the real economy is also in an important period of high-quality development. Promoting the organic integration of manufacturing industry and digital economy to achieve high-quality development is a key and difficult problem to be solved. This paper examines the impact of digital economy on the high-quality development of manufacturing industry, the action mechanism and possible regional heterogeneity of the influence based on a panel dataset of 31 Chinese provinces and cities. The results show that digital economy can significantly promote the high-quality development of manufacturing industry, technological innovation and management efficiency have played positive intermediary roles in the relationship, furthermore,the technological innovation has a greater intermediary effect. There is regional heterogeneity about this impact, for example, the promotion effect in the eastern, western and southern regions is more significant than that in the center and north. At the time when China’s economic growth is transforming the old and new kinetic energy, more attention should be paid to the construction of infrastructure related to the development of digital economy, to promote the development of digital economy according to local conditions, to cultivate innovation platforms, to strengthen the training of digital technology talents, to promote digital industrialization and industrial digitalization, and to achieve high‐quality development of the manufacturing industry.