International institutions are increasingly being challenged by domestic opposition and nationalist political forces. Yet, levels of politicization differ significantly across countries facing the same international authority as well as within countries over time. This raises the question of when and why the mass public poses a challenge to international cooperation. In this article, we develop a theoretical framework for understanding the nature and implications of politicization of international cooperation, outlining three scope conditions: the nature of public contestation, the activities of political entrepreneurs, and the permissiveness of political opportunity structures. By empirically examining these scope conditions, we demonstrate that politicization can have both stabilizing and destabilizing effects on international cooperation. Highlighting the systemic implications of politicization for international cooperation has important implications for international relations scholarship. Although international organizations may face challenges, they also have ways of being remarkably resilient.