<p>Amid the accelerating transformation toward a digital economy, new digital infrastructure has become a vital driver of entrepreneurship. This study constructs a panel dataset of 278 prefecture-level cities in China, using data from 2009 to 2020. The new digital infrastructure level is measured using a big data text analysis approach that is based on local government work reports. In addition, using patent co-application data, this study builds multi-level innovation cooperation networks by capturing both intra-city and inter-city connections. This paper systematically evaluates the direct impact of new digital infrastructure on entrepreneurship, as well as the digital infrastructure’s indirect effect through innovation collaboration networks. The empirical results indicate that new digital infrastructure significantly enhances entrepreneurship. In addition, this effect is partially mediated by the formation of intra- and inter-city innovation cooperation networks. Heterogeneity analyses reveal that the positive effect is more pronounced in technology-intensive industries, provincial capital cities, and cities with low dialectal diversity. Further analysis suggests that the development of new infrastructure spur an increase in venture capital investment. The findings offer important policy implications for building regionally adaptive and digitally driven entrepreneurial ecosystems.</p>