This paper argues that a certain level of indeterminacy in policy design may be a factor facilitating rather than hindering system-level change in welfare governance arrangements, provided it is combined with the triggering of specific concatenations of social mechanisms shaping the dynamics of the change process. The argument is illustrated by an analysis of a case of systemic change in chronic disease management occurred in the Italian region of Lombardy over 2016–2017, when a radically novel governance of chronic disease for the 10 million population was put in place (a health care system that was later tested to its limits by the COVID-19 pandemic outburst which reached dramatic intensity in this region). This represented a major change in a key area of social and health policy. We claim that such change processes may be studied by means of the conceptual tools of social mechanisms. The analysis of social mechanisms represents a lively research agenda for explaining change in public governance and public policy.