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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., Competing Interests: The authors have read the journal’s policy and have the following competing interests: This study is part of a consortium research project between Stockholm Resilience Centre and the Ellen MacArthur Foundation, initiated and funded indirectly by H&M Group, the Swedish public limited company and a Strategic Partner in the Ellen MacArthur Foundation’s global network for circular economy. The employment of JH, CP, and SC was partially funded through this project. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.