Drawing on a novel theoretical framework, we explored the impact of research and development (R&D) effort on business model innovation via external collaboration breadth and collaboration depth in sequence. We empirically analyzed a sample of 94 Chinese innovative enterprises by applying hierarchical regression analysis andchain mediationanalysis. The results indicate that R&D effort positively influences business model innovation. The influencing mechanism is that R&D effort positively affects external collaboration breadth, which in turn positively stimulates external collaboration depth, and ultimately benefits the implementation of business model innovation. Therefore, the breadth and depth of external collaboration play a chain-mediating role. The study develops a new framework for understanding the relationship between R&D effort, external collaboration, and business model innovation. It combines enterprises’ internal behavior (R&D) and external behavior (collaboration) to establish an inside-out mechanism for predicting business model innovation. It enriches the theory of business model innovation. It also provides insights for managers and governments to optimize policies in innovation-driven development.