Urban adaptation to climate change is a global challenge requiring a broad response that can be informed by how urban societies in the past responded to environmental shocks. Yet, interdisciplinary efforts to leverage insights from the urban past have been stymied by disciplinary silos and entrenched misconceptions regarding the nature and diversity of premodern human settlements and institutions, especially in the case of prehispanic Mesoamerica. Long recognized as a distinct cultural region, prehispanic Mesoamerica was the setting for one of the world’s original urbanization episodes despite the impediments to communication and resource extraction due to the lack of beasts of burden and wheeled transport, and the limited and relatively late use of metal implements. Our knowledge of prehispanic urbanism in Mesoamerica has been significantly enhanced over the past two decades due to significant advances in excavating, analyzing, and contextualizing archaeological materials. We now understand that Mesoamerican urbanism was as much a story about resilience and adaptation to environmental change as it was about collapse. Here we call for a dialogue among Mesoamerican urban archaeologists, sustainability scientists, and researchers interested in urban adaptation to climate change through a synthetic perspective on the organizational diversity of urbanism. Such a dialogue, seeking insights into what facilitates and hinders urban adaptation to environmental change, can be animated by shifting the long-held emphasis on failure and collapse to a more empirically grounded account of resilience and the factors that fostered adaptation and sustainability.