Little is known about how division of labor and coordination unfold in partnerships addressing grand challenges, where no one has formal authority to direct efforts. This study examines how goal-frames direct the division of labor and coordination in grand challenge partnerships, leveraging longitudinal data on a Swedish-based GC-partnership with the system-level goal of transforming cancer from a deadly to a curable or chronic disease. We develop a process model of how discrete “behavioral modes” of dividing labor and coordinating efforts, with different skill-related coordination cost properties, via two behavioral mechanisms – jointholism and relational blindness – can result in deteriorating cooperation. Our model provides a behavioral foundational explanation for why grand challenge partnerships frequently fail to meet expectations and remain viable.