The COVID-19 pandemic highlighted the importance of strengthening collaborations between academia and government. The development and maintenance of these collaborative relationships is a complex and dynamic process, particularly during public health emergencies. This study was aimed at identifying and analyzing factors that acted as barriers and facilitators in the collaboration process between academia and government during the COVID-19 pandemic in the five largest cities in Colombia. The study used a qualitative approach based on the systematization of experiences. Twenty-five semi-structured interviews were conducted with local actors from government and academia during 2021. Participants identified a variety of situations that involved individual, institutional and relational factors that acted as barriers and facilitators, and which have been previously reported in other countries and contexts not related to pandemics. Based on participant reports, two additional factors emerged, one corresponding to situations related to the pandemic management process itself and another related to structural or systemic conditions that involved government processes and the Colombian health system. Despite the challenges posed by the pandemic, the health emergency brought about shared feelings of local commitment and a willingness to work through interdisciplinary teams to address the pandemic with the least adverse effects on the community. Other facilitators of the collaborative process that were recognized were the importance of timely access to data and transparent analyses, as well as government decisions being informed by the perspectives of academics. The main barriers identified by both actors were excessive centralization of the pandemic’s management and the need for rapid decision-making processes under high levels of uncertainty. In addition, the fragmentation of services in the health system posed a barrier to the interventions that were suggested by the collaborative work. Our results suggest that government-academia collaborations should be implemented as ongoing participatory processes integrating various sectors, actors and disciplines.