As the construction of Digital China continues to deepen, comprehensive digital transformation has emerged as a key strategic direction for supporting high-quality economic and social development and advancing Chinese modernization. By applying systematic thinking, comprehensive digital transformation overcomes the limitations of single-point technological upgrades and enables the construction of a collaborative development system across regions, departments, and sectors, thereby injecting strong momentum into the construction of Digital China. However, many regions in China currently face prominent challenges such as widespread data silos, insufficient coverage of business scenarios, and weak innovation supply capacity. Relying solely on piecemeal technological breakthroughs cannot fundamentally resolve these transformation bottlenecks. Therefore, accelerating the development of an efficient and smooth technology factor circulation system has become an urgent priority. As an emerging concept, comprehensive digital transformation remains in the preliminary stage of research, with a notable lack of quantitative empirical analysis at the macro-regional level and a particular scarcity of systematic identification and examination of its influencing mechanisms. Using panel data from 30 Chinese provinces from 2012 to 2024, this study treats the establishment of National Technology Transfer Centers as a quasi-natural experiment and employs a staggered difference-in-differences (DID) model to systematically examine the impact of technology transfer on comprehensive digital transformation from a knowledge spillover perspective. It further investigates the synergistic effects of digital economy-related policies. The empirical results show the following. First, the establishment of National Technology Transfer Centers significantly enhances the level of comprehensive digital transformation in host regions and effectively alleviates the practical dilemmas of “daring not to transform, lacking the know-how to transform, and failing to transform well” that characterize the process. Second, technology transfer primarily drives this transformation through knowledge spillover effects, with knowledge flow, knowledge absorption, and knowledge accumulation serving as three transmission channels. Third, digital government policies, digital technology policies, and data factor policies all exhibit significant synergistic effects with technology transfer centers, which amplify the positive impact on comprehensive digital transformation. Fourth, the promoting effect of technology transfer on comprehensive digital transformation is more pronounced in regions with a stronger transformation foundation, a higher level of industrial structure upgrading, and a greater degree of marketization. Based on these findings, this paper proposes four policy recommendations: optimizing the spatial layout of technology transfer centers to activate transformation momentum; unblocking knowledge spillover channels to enhance the efficiency of knowledge flow, absorption, and accumulation; promoting digital policy synergy to explore new paradigms for digital governance of technology transfer; and implementing differentiated strategies to fully leverage the driving effects of these centers. Compared with existing studies, the marginal contributions of this paper are threefold. First, it constructs an indicator system for comprehensive digital transformation from a full-cycle perspective of “conditions-process-outcomes,” thereby expanding the quantitative boundaries of research in this field. Second, by using the establishment of National Technology Transfer Centers as a quasi-natural experiment, it systematically evaluates the impact of technology transfer on comprehensive digital transformation, providing both new theoretical insights and empirical evidence on the economic consequences of technology transfer. Third, from the knowledge spillover perspective, it sequentially examines the three mechanisms of knowledge flow, knowledge absorption, and knowledge accumulation, revealing the “black box” of how technology transfer empowers comprehensive digital transformation. Furthermore, it tests the synergistic empowering effects of digital economy policies from three dimensions of digital government, digital technology, and data factors, providing solid empirical support for better leveraging the role of a capable government in promoting comprehensive digital transformation in the new era.