Enhancing regional innovation efficiency is of great significance for accelerating regional high-quality development and building an innovative country. Based on the perspective of innovation ecosystem, this study constructs a regional innovation ecosystem analytical framework by integrating six key regional innovation ecosystem elements from three aspects: innovation actor, innovation resource, and innovation environment. Using a sample of 30 provinces in China and adopting methods such as NCA and fsQCA, this paper analyzes the multiple pathways of regional innovation ecosystem on regional innovation efficiency in two stages froma configurational perspective. The study results in several findings. Firstly, a single element of the regional innovation ecosystem does not constitute the necessary condition either for high R&D efficiency or for high commercialization efficiency, though high innovation-actor-link generally plays a universal role in achieving high R&D efficiency. Secondly, there are three pathways to achieve high R&D efficiency and five pathways to achieve high commercialization efficiency. Great differences exist between these two types of regional innovation efficiency pathways: strong innovation-actor-link plays a more crucial role in achieving high R&D efficiency, while favorable innovation-supportive-environment is more important for achieving high commercialization efficiency. Besides, the distribution of the cases with high R&D efficiency exhibits distinct spatial distribution characteristic. Thirdly, based on the intersection operation of the two types of high innovation efficiency configurations, we find that three pathways can achieve both high R&D efficiencies and high commercialization efficiencies. Among the 6 typical cases, 4 provinces are in eastern China. Finally, based on further discussion and analysis, three meaningful research propositions for future exploration are proposed. Overall, this work refines the theoretical analysis framework of regional innovation ecosystem and deepens the analysis of the complex causal relationship between regional innovation ecosystem and innovation efficiency, and provides policy implications for regions to improve innovation efficiency from the perspective of innovation ecosystem.