The socio-ecological realities of anthropic origin facing humanity in the twenty-first century have been configured in scientific, political, economic, and ethical challenges that put human and planetary health at risk. The climate emergency, the accelerated loss of biodiversity, and the high levels of pollution, especially in the form of novel entities and biogeochemical alterations, pose the need for urgent collective action that transcends rationalities centered on individualism, competition, and command and control approaches to socio-ecological impacts, toward those based on critical awareness, reciprocity, and the global common good. Higher education institutions (HEIs) are key actors in addressing these challenges through their substantive functions: teaching, research, and the extension of knowledge and culture. The purpose of this chapter is to critically analyze the importance of the commons generated and cared for by HEIs and their political relevance in view of the complex socio-ecological challenges humanity faces. To this end, the conditions in which the common good is produced by HEIs are first analyzed. A need for profound institutional changes in HEIs—including the generalized adoption of transdisciplinary, situated, political, and epistemological approaches to teaching, research, outreach, and campus governance—is identified, as a requisite to accelerate the contribution of higher education to structural transformations toward an ecological and socially just civilization. The chapter concludes with a series of proposals for HEIs to foster articulated actions to face current and future socio-ecological realities.