Academic medical centers could play an important role in increasing access to and uptake of SARS-CoV-2 vaccines, especially in Black and Latino communities that have been disproportionately affected by the pandemic. This article describes the vaccination program developed by the Boston Medical Center (BMC) health system (New England’s largest safety-net health system), its affiliated community health centers (CHCs), and community partners. The program was based on a conceptual framework for community interventions and aimed to increase equitable access to vaccination in the hardest-hit communities through community-based sites in churches and community centers, mobile vaccination events, and vaccination on the BMC campus. Key strategies included a communication campaign featuring trusted messengers, a focus on health equity, established partnerships with community leaders and CHCs, and strong collaboration with local health departments and the Commonwealth of Massachusetts to ensure equitable allocation of the vaccine supply. Process factors involved the use of robust analytics relying on the Centers for Disease Control and Prevention’s Social Vulnerability Index (SVI). The vaccination program administered 109 938 first doses, with 94 703 (86%) given at community sites and 2466 (2%) given at mobile sites. Mobile vaccination events were key in reaching younger people living in locations with the highest SVIs. Challenges included the need for a robust operational infrastructure and mistrust of the health system given the long history of economic disinvestment in the surrounding community. The BMC model could serve as a blueprint for other medical centers interested in implementing programs aimed at increasing vaccine uptake during a pandemic and in developing an infrastructure to address other health-related disparities.