Migratory tundra caribou are ecologically and culturally critical in the circumpolar North. However, they are declining almost everywhere in North America, probably due to natural variation exacerbated by climate change and human activities. Yet, the interconnectedness between climate, caribou and human well-being has received little attention. To address this gap, we bridged Indigenous and scientific knowledge in a single model, using as example the Porcupine caribou herd social-ecological system. Our analysis, involving 688 (fall season) and 616 (spring season) interviews conducted over 9 years with 405 (fall season) and 390 (spring season) Indigenous hunters from 9 communities, demonstrates that environmental conditions, large-scale temporal changes associated with caribou demography and cultural practices affect hunters’ capacity to meet their needs in caribou. Our quantitative approach bolsters our understanding of the complex relationships between ecosystems and human welfare in environments exposed to rapid climate change and shows the benefits of long-term participatory research methods implemented by Indigenous and scientific partners.