Recent years have witnessed ongoing technological blockades of developed countries against China, making major breakthroughs in core technologies has elevated to a national strategic level. Chinese manufacturing companies ‘dependence on foreign technology’ put them at a disadvantage when compete in the global marketplace, raising the importance of exploring the key factors behind their breakthrough of core technology. This study adopted multiple case studies to reveal the successful factors of achieving major breakthroughs in key core technologies from the point view of the main drivers of innovation, that is China leading manufacturing companies. The results showed that a mix of internal and external factors were considered which favor the breakthrough of key core technologies. For China leading manufacturing companies, the internal factors influencing their major breakthroughs were such factors as innovation strategy, R D investment, technology accumulation, advanced talents, R D systems, the external factors were market competition and government support. Our results provided practical, evidence-based guidance on how China leading manufacturing companies grasped key core technologies.