Regional collaborative innovation is essential for realizing the Chinese path to modernization. Based on the panel data of 276 cities in China from 2008 to 2018, this paper takes the National Smart City pilot policy as the quasi-natural experiment to explore the collaborative innovation effect and its mechanism of smart city construction. The results show that smart city pilot policies significantly promote regional collaborative innovation. The implementation of this policy increases the number of regional cooperative patents (per 10,000 people) in the pilot cities by about 0.479. Improving local innovation capabilities and developing high-tech industries are two important mechanisms for smart city construction to promote regional collaborative innovation. Further analysis reveals that the construction of smart cities has a greater impact on cities with good location conditions, and this impact is also related to the size of the city. This paper provides an essential reference for further promoting smart city pilot policies across the country and provides a new idea for accelerating regional collaborative innovation.