The multi-level perspective has successfully been applied to the analysis of complex sector transitions in the energy, the health or the food production sector. Is this framework also helpful to understand and give prescriptive advice for sustainability transformations within a national science system? Based on a comprehensive study of the diffusion of transdisciplinary sustainability research in Germany, this article analyzes the institutional dimension of a changing science-society relation in the German science system. It uses the multi-level perspective as a fruitful heuristic in order to identify potential pathways for a broader diffusion of transdisciplinary sustainability science. The importance of niche coalitions of frontrunner universities and research institutes are highlighted.