The integration of the digital and real economy driven by innovation is not only the key to promoting China’s “smart manufacturing” transformation and cultivating new quality productive forces, but also an important way to seize the strategic high ground in the digital economy landscape. Based on the provincial panel data in China from 2013 to 2022, this paper empirically tests the impact and mechanism of innovation factor flow on the regional integration of the digital and real economy. The results are as follows: First, innovation factor flow can significantly improve regional integration of the digital and real economy, which is still true after a series of robustness tests. Heterogeneity analysis reveals that there are regional and temporal differences in this effect, which is more pronounced in the central and western regions and after the introduction of the national innovation-driven development strategy. Second, the mechanism testing shows that the flow of innovative factors builds a digital service industry ecosystem and expands digital technology application scenarios through industrial structure transformation, thereby promoting the regional integration of the digital and real economy. Third, given the cross-regional flow characteristics of innovation factors, this paper further constructs a dynamic spatial Durbin model and finds that the flow of innovation factors not only improves the local integration of the digital and real economy but also produces spatial spillovers to adjacent regions. Specifically, the flow of innovative talents significantly enhances local integration of the digital economy and real economy in the short term and spills over to surrounding areas; The flow of innovative capital has a time lag, and its promoting effect is more pronounced in the long run; The flow of data elements has a dual temporal characteristic, that is, it plays a positive role in the short term, but has a negative direct effect in the long run. Research on innovation-driven integration of the digital and real economy provides empirical evidence for the in-depth implementation of innovation-driven development strategies, promoting the coordinated development of digital industrialization and industrial digitization, and winning the initiative in development.