Higher education institutions (HEIs) have been steadily progressing towards the integration of sustainable practices in their structures and operations. Several studies have reported the variety of drivers of change and the barriers to change that universities have found in the integration process. The present investigation is aimed at further characterizing and ranking the drivers for, and barriers of, sustainability integration in HEIs within their structures and operating functions. Open-ended expert opinion interviews of key sustainability leaders appointed at 45 HEIs from 10 Latin-American countries were conducted in order to learn lessons from their diverse experiences of the process. Additionally, a thematic workshop on HEI sustainability was organized to facilitate further discussions between 23 sustainability scholars and/or national coordinators of university networks from 11 Latin American countries. As a result, 15 barriers were identified as hindering the institutionalization of sustainability in HEIs. This study also examined the relationship between these reported barriers with 13 main drivers that were identified to be facilitating the integration of sustainable practices within the organizational and academic structures at the universities. The strong correspondence between the several observed drivers for, and barriers to, change highlights the importance of strategic planning that offers integrated actions. The findings of this paper can serve as a reference to assist HEIs in identifying drivers of, and barriers to, sustainability, so that the former can be fostered and the latter addressed effectively. This can help identify and plan targeted actions to make the transition towards sustainability in HEIs more natural and effective.