Abstract Context Relationships between researchers and decision-makers have demonstrated positive potential to influence research, policy and practice. Over time, interest in better understanding the relationships between the two parties has grown as demonstrated by a plethora of studies globally. However, what remains elusive is the evolution of these vital relationships and what can be learned from them with respect to advancing evidence-informed decision-making. We therefore explored the nuances around the initiation, maintenance and dissolution of academic–government relationships. Methods We conducted in-depth interviews with 52 faculty at one school of public health and 24 government decision-makers at city, state, federal and global levels. Interviews were transcribed and coded deductively and inductively using Atlas.Ti. Responses across codes and respondents were extracted into an Excel matrix and compared in order to identify key themes. Findings Eight key drivers to engagement were identified, namely (1) decision-maker research needs, (2) learning, (3) access to resources, (4) student opportunities, (5) capacity strengthening, (6) strategic positioning, (7) institutional conditionalities, and (8) funder conditionalities. There were several elements that enabled initiation of relationships, including the role of faculty members in the decision-making process, individual attributes and reputation, institutional reputation, social capital, and the role of funders. Maintenance of partnerships was dependent on factors such as synergistic collaboration (i.e. both benefit), mutual trust, contractual issues and funding. Dissolution of relationships resulted from champions changing/leaving positions, engagement in transactional relationships, or limited mutual trust and respect. Conclusions As universities and government agencies establish relationships and utilise opportunities to share ideas, envision change together, and leverage their collaborations to use evidence to inform decision-making, a new modus operandi becomes possible. Embracing the individual, institutional, networked and systems dynamics of relationships can lead to new practices, alternate approaches and transformative change. Government agencies, schools of public health and higher education institutions more broadly, should pay deliberate attention to identifying and managing the various drivers, enablers and disablers for relationship initiation and resilience in order to promote more evidence-informed decision-making.