Vaccination disparities are part of a larger system of health inequities among racial and ethnic groups in the United States. To increase vaccine equity of racial and ethnic populations, the Centers for Disease Control and Prevention (CDC) designed the Partnering for Vaccine Equity program in January 2021, which funded and supported national, state, local, and community organizations in 50 states-which include Indian Health Service Tribal Areas; Washington, DC; and Puerto Rico-to implement culturally tailored activities to improve access to, availability of, and confidence in COVID-19 and influenza vaccines. To increase vaccine uptake at the local level, CDC partnered with national organizations such as the National Urban League and Asian & Pacific Islander American Health Forum to engage community-based organizations to take action. Lessons learned from the program include the importance of directly supporting and engaging with the community, providing tailored messages and access to vaccines to reach communities where they are, training messengers who are trusted by those in the community, and providing support to funded partners through trainings on program design and implementation that can be institutionalized and sustained beyond the COVID-19 pandemic. Building on these lessons will ensure CDC and other public health partners can continue to advance vaccine equity, increase vaccine uptake, improve health outcomes, and build trust with communities as part of a comprehensive adult immunization infrastructure.