From the start of the COVID-19 pandemic on the Navajo Nation, Diné (Navajo) traditional knowledge holders (TKHs), such as medicine men and women and traditional practitioners, contributed their services and healing practices. Although TKHs are not always fully acknowledged in the western health care system, they have an established role to protect and promote the health of Diné people. To date, their roles in mitigating the COVID-19 pandemic have not been fully explored. The purpose of this research was to understand the social and cultural contexts of the COVID-19 pandemic and vaccines based on the roles and perspectives of Diné TKHs. A multi-investigator consensus analysis was conducted by six American Indian researchers using interviews with TKHs collected between December 2021–January 2022. The Hózhó Resilience Model was used as a framework to analyze the data using four parent themes: COVID-19, harmony and relationships, spirituality, and respect for self and discipline. These parent themes were further organized into promoters and/or barriers for 12 sub-themes that emerged from the data, such as traditional knowledge, Diné identity, and vaccine. Overall, the analysis showed key factors that could be applied in pandemic planning and public health mitigation efforts based on the cultural perspective of TKHs.