The Medical College of Wisconsin (MCW) serves the Milwaukee metro area, one of the most diverse and segregated urban areas in the United States. In the acute crisis phase of the COVID-19 pandemic, MCW’s Civic and Community Engagement (C/CE) efforts were leveraged to address community concerns around four key initiatives: (a) availability of personal protective equipment in community; (b) food and housing issues for homeless individuals; (c) the need for multi-lingual, culturally tailored public health information around infection control through work with artists, influencers, and community health workers; and (d) later, addressing vaccination disparities and fears in an equitable way. These efforts were undertaken in collaboration with the City of Milwaukee Health Department, the Milwaukee County Office of African American Affairs, and other external partners. A multi-actor case study approach examined the intersection of Institutions of Higher Education, government, and community—with a particular emphasis on how Schools of Medicine can serve a unique role in bridging these domains to create a more robust framework for equitable, humanistically informed community crisis response. Implications for future public health disasters, as well as institutional civic engagement in response to pervasive, day-to-day problems around upstream determinants of health are explored.