Global industries are typically dominated by a few disproportionately large and influential transnational corporations, or keystone actors. While concentration of economic production is not a new phenomenon, in an increasingly interconnected and globalized world, the scale of the impacts of keystone actors on diverse social-ecological systems continues to grow. In this article, we investigate how keystone actors in the global clothing industry engage in collaboration with a variety of other organizations to address nine interrelated biophysical and socioeconomic sustainability challenges. We expand on previous theoretical and empirical research by focusing on the larger business ecosystem in which keystone actors are embedded, and use network analysis to assess the contributions of different actor types to the architecture of the ecosystem. This systemic approach to the study of keystone actors and sustainability challenges highlights an important source of influence largely not addressed in previous research: the presence of organizations that occupy strategic positions around keystone actors. Such knowledge can help identify governance strategies for advancing industry-wide transformation towards sustainability.