Abstract: Enterprises are the micro-foundation of the national innovation system, the vanguard in building the capacity for industrial technology innovation, and the core agent in accelerating the development of new forms of productive forces. This paper, beginning with the current demands for and the practical foundation of the paradigm shift towards enterprise-led industrial science and technology (S&T) innovation, analyzes the theoretical and practical logic behind the transformation of technology enterprises from “technology innovation” subjects to “S&T innovation” subjects, and their leading role in technological and industrial innovation. It reviews international experience that supports enterprises in spearheading the construction of a modern industrial system and the implications for China's rapid development of new quality productivity. Further, it puts forward policy recommendations centered on strengthening the enterprise-led industrial S&T innovation system and accelerating the development of new quality productivity, including nurturing and developing technology-leading enterprises, improving the new national system, enhancing deep integration of industry-academia-research led by enterprises, seizing opportunities from context-driven innovation paradigm, supporting the development of digital platform enterprises, and stimulating the innovation dynamism of the whole society.