The reconstruction of diet, subsistence strategies and human-animal relationships are integral to understanding past human societies, adaptations and resilience - especially in the circumpolar Arctic. Even in relatively recent periods, climatic excursions may have posed specific challenges for hunter-gatherer groups living at latitudinal and climatic extremes, and archaeological research in Arctic North America is increasingly looking to better understand the impact of past climate change on human groups. Here, through a unique multi-proxy approach (zooarchaeology, bone technology and stable isotope analysis), we explore human subsistence strategies, adaptation and resilience at Nunalleq, a recently excavated pre-contact Yup'ik coastal site in southwest Alaska. The main phase of occupation of the site (16th-17th centuries AD) corresponds with one of the coolest periods of the Little Ice Age – a climatic interval from the early 14th century through the mid-19th associated with global and more localised cooling events. The analyses reveal a subsistence strategy centred around the exploitation of three major resources, including salmon, marine mammals and caribou, supplemented by secondary resources such as birds and medium-sized mammals. This tripartite resource base (salmon, marine mammals, caribou) is similar to that seen at other Thule-era sites in Alaska and likely permitted a flexibility in resource use in the face of changes in resource availability (and competition over resources) during the Little Ice Age. Comparison of the different datasets, however, reveals variability and nuance in the use of animals for both dietary and broader subsistence needs. While caribou represent a vital and heavily-exploited resource at Nunalleq (evident from both the zooarchaeology and the bone technology), they did not represent a key dietary resource (indicated by stable isotope data). Instead, caribou played an integral and key part as a major source of raw material, especially antler, in order to manufacture the necessary acquisition technology to exploit primary coastal resources.