The COVID-19 pandemic has disproportionately affected Indigenous peoples from a health, economic, and spiritual perspective, threatening the survival of elders and the perpetuation of culture, which is vital for well-being. Despite layered challenges, Indigenous communities showed remarkable agility and resilience. A panel discussion will bring together Indigenous and allied physicians and public health leaders from the U.S. and Australia to discuss lessons learned from engaging communities to overcome programmatic hurdles and encourage the uptake of COVID-19 vaccines for populations across the life course.