We investigate the perceptions and impacts of climate change on 11 Indigenous communities in Northern British Columbia and Southeast Alaska. This coastal region constitutes an extremely dynamic and resilient social-ecological system where Indigenous Peoples have been adjusting to changing climate and biodiversity for millennia. The region is a bellwether for biodiversity changes in coastal, forest, and montane environments that link the arctic to more southerly latitudes on the Pacific coast. Ninety-six Elders and resource users were interviewed to record Traditional Ecological Knowledge (TEK) and observations regarding weather, landscape, and resource changes, especially as concerns what we term Cultural Keystone Indicator Species (CKIS), which provide a unique lens into the effects of environmental change. Our findings show that Indigenous residents of these communities are aware of significant environmental changes over their lifetimes, and an acceleration in changes over the last 15–20 years, not only in weather patterns, but also in the behaviour, distributions, and availability of important plants and animals. Within a broader ecological and social context of dwelling, we suggest ways this knowledge can assist communities in responding to future environmental changes using a range of place-based adaptation modes.