Leading with big data to promote science and technology innovation is a key part of the implementation of the big data strategy action. Based on Chinese urban panel data from 2007 to 2019, the impact of digital technology on science and technology innovation is systematically analyzed through a multi-period double difference model based on a quasi-natural experiment in a national-level comprehensive big data test area from both theoretical and empirical perspectives. A series of robustness tests were performed to demonstrate the reliability of the results. The results of the study show that enhancing digital technology can significantly promote the level of science and technology innovation, and the intensity of the role of digital technology is regionally heterogeneous, showing southern region > northern region and high administrative level cities > general municipalities. Based on the above results, the following insights are proposed: promoting the construction of big data pilot zones, optimizing the innovation system environment, improve the talent flow mechanism, and giving full play to the role of digital technology in promoting science and technology innovation.