This study, based on panel data from 31 provinces in China from 2017 to 2021, evaluates the technical efficiency, pure technical efficiency, and scale efficiency of university science and technology innovation (STI) using a three-stage DEA model, considering the characteristics of the university STI process and the impact of non-managerial factors. It further investigates the influencing factors on the efficiency of university STI through Tobit regression analysis. The results indicate an overall upward trend in the efficiency of university STI across China, with a regional disparity pattern of “highest in the northeast, followed by the central region, then the east, and lowest in the west”. Scale efficiency is identified as a primary factor affecting the technical efficiency of university STI. The economic environment and policy support negatively impact input efficiency, whereas the level of industrial structure has a positive impact. Personnel structure, talent cultivation, and internationalization level are important factors for improving the efficiency of university STI. High investment does not necessarily result in high efficiency and optimizing the funding management system is essential for government support and industry-academic cooperation.