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Climate change is causing widespread impacts to hydrological systems and altering ecosystems across the circumpolar north. Indigenous peoples have a rich knowledge of environmental changes in their territories and the social-ecological impacts of shifting conditions, which can inform our understanding of how these systems are changing. In this study, we used a participatory, mixed methods approach (29 interviews, 32 questionnaires) to synthesize Gwich’in and Inuvialuit knowledge of hydrological changes observed in the Mackenzie Delta Region. There was a strong consensus among Indigenous knowledge holders that an observed reduction in water levels is linked to increases in permafrost mass wasting, riverbank erosion, and sandbar formation. Indigenous knowledge holders also noted that shifting hydrology has disrupted travel and fishing activities in ways that are likely to impact the health and well-being of Indigenous communities in the region. These findings demonstrate that collaborative partnerships with Indigenous knowledge holders are critical to effectively identify regional-scale environmental change, understand its socioecological impacts, and support local and regional decision-making. Interview participants also highlighted the importance of on-the-land education and intergenerational knowledge sharing to ensure youth can continue to care for the land in the face of rapid socio-ecological change.