<p>Despite a growing body of literature on entrepreneurial ecosystems (EEs), little is known about how ecosystem orchestration occurs. Building on the theoretical foundations of transactive memory systems (TMS), we propose a conceptual framework to explain the potential role of an ecosystem-wide TMS in facilitating ecosystem orchestration through learning. Drawing upon insights from two streams of literature: (i) the structure, process, and knowledge characteristics of the TMS and (ii) the 4I organizational learning framework, we delineate the orchestration role of such a TMS. Ecosystem actors can leverage their organizational-level TMS to help build a TMS at the ecosystem level. In turn, the ecosystem-wide TMS serves as a primary mechanism for orchestrating the ecosystem, based on learning within and among ecosystem actors. The resulting TMS-based process framework, along with the series of testable propositions we offer, can provide pathways for future empirical research on EE evolution and change. Plain English Summary When entrepreneurs and other actors in the entrepreneurial ecosystem (EE) collaborate, they exchange knowledge, information, and other network resources. At the same time, given the dynamic and voluntary nature of these arrangements, governance challenges arise. Therefore, what becomes extremely important is that a collective memory system develops that spans the entire ecosystem and functions effectively. This is an ecosystem-wide transactive memory system (TMS). It serves as the “brain” of the ecosystem. Even though the TMS offers many benefits, it can also be highly challenging for actors to operate, especially due to the ensuing complexities associated with the memory system’s structure, processes, and the knowledge to be exchanged. We offer a conceptual framework and a set of guidelines that can help entrepreneurs and other ecosystem actors engage in such endeavors in an effective and supportive way, leading the ecosystem to transform and succeed.</p>