The Arctic has been home to Indigenous Peoples from time immemorial. Distinct Indigenous worldviews and complex knowledge systems have been passed on from generation to generation, evolving over time in a living process that continues to this day. Indigenous Peoples' knowledge systems hold methodologies and assessment processes that provide pathways for knowing and understanding the Arctic, which address all aspects of life, including the spiritual, cultural, and ecological, all in interlinked and supporting ways. For too long, Indigenous Peoples of the Arctic and their knowledges have not been equitably included in many research activities. We argue for systematic change in how research-related activities are conducted in the Arctic. Bringing together multiple knowledge systems, specifically Indigenous Peoples' knowledge systems and science, can lead to more equitable, inclusive, and useful outcomes. The co-production of knowledge framework that we forward is designed to assist researchers, decision makers, and communities in moving toward those goals. Given increased interest in the Arctic by the research community, the complex, rapid, and ongoing change in Arctic systems, and amidst renewed and urgent calls for equity globally and across all spheres of life, adoption of a co-production of knowledge framework for the conduct of Arctic research is timely as well as a moral and intellectual imperative. Further, solutions to challenges facing the Arctic and global community are enhanced by the combined understanding of Indigenous Peoples' knowledges and science.