Formal recognition of the cultural significance of freshwater species to Indigenous people is an important part of equitable ecosystem management that bridges gaps in our culturally sensitive management of these critical species and builds cross-cultural relationships. Indigenous peoples of Australia, North America, and New Zealand have a long tradition of harvesting freshwater animals over thousands of generations, and their profound understanding of these freshwater animals and ecosystems have become embedded within their cultural identity. In recognizing such cultural connections, we can all better appreciate the deep significance of changes in the conservation and management of freshwater animals for Indigenous peoples, and work to integrate Indigenous stewardship and ecological knowledge into effective co-management strategies (e.g., Indigenous rangers, research partnerships, Indigenous Protected Areas). We recommend that future policy developments should explicitly incorporate Cultural Keystone Species (CKS), which are species that support both Indigenous cultural identity and key freshwater ecosystem processes. Moreover, CKS can provide focal points for promoting positive policy outcomes that empower Indigenous people and develop innovative management and monitoring programs. In drawing on the understanding of eight Indigenous authors from across Australia, North America, and New Zealand, we reviewed and highlighted the importance of several freshwater CKS, many of which are of trans-Pacific importance. Our hope is that greater emphasis on the equitable management of these CKS will improve the health and wellbeing of the social and ecological components of freshwater ecosystems across the world.