Climate change directly threatens human health, with substantial impacts on Indigenous peoples, who are uniquely vulnerable as climate-related events affect their practices, lifeways, self-determination, and physical and cultural health. At the same time, Indigenous communities are leading the way in innovative health-related climate change adaptation work, using traditional knowledges and novel approaches. In 2016 the Centers for Disease Control and Prevention and the National Indian Health Board created the Climate-Ready Tribes Initiative to support these efforts. The initiative has funded tribes, shared information nationally, and supported a learning cohort, resulting in pioneering work to protect health from climate hazards. We describe how two tribes-the Pala Band of Mission Indians and the Swinomish Indian Tribal Community-implemented their Climate-Ready Tribes Initiative projects, and we provide recommendations for making climate and health policy more effective for tribes. Lessons learned from the Climate-Ready Tribes Initiative can inform climate and health policy and practice nationwide.