Ongoing tensions between Indigenous and non-Indigenous communities working in support of the protection and management of fish and water in North America have necessitated a shift from current structures towards relationships built upon and driven by respect, relevance, reciprocity, and responsibility. Similarly, the cumulative and evolving effects of climate change, industrialization, resource extraction, and displacement of Indigenous Peoples from their traditional and contemporary lands and waters requires purposeful application of decolonizing methods in aquatic systems management and protection, which in turn aids in the re-establishment of agency to Indigenous Peoples. This article endeavors to outline critical differences in ‘best practices’ and ‘wise practices’ in Laurentian Great Lakes fisheries management, water protection, and Indigenous-settler working relations through dialogue on experiences of Indigenous working relationships with colonial governmental bodies. We discuss critical misunderstandings, and the need for creating room for and profoundly respecting Indigenous ways of knowing and being. This work brings together lessons, stories, and knowledge from a panel of Indigenous and allied scholars and community members from the International Association for Great Lakes Research annual conference in May 2021, and subsequently uses a conversation-based methodology to preserve the voices and teachings of panelists. The lessons shared in this work are vital to the future of Laurentian Great Lakes fish and water health.