Significance The peopling of the Americas has been examined on the continental level with the aid of SNP arrays, next generation sequencing, and advancements in ancient DNA, all of which have helped elucidate evolutionary histories. Regional paleogenomic studies, however, have received less attention and may reveal a more nuanced demographic history. We present genome-wide sequences of individuals from the northern Northwest Coast covering a timespan of ∼10,000 years and show that continental patterns of demography do not necessarily apply on the regional level. Compared with existing paleogenomic data, we show that geographically linked population samples from the Northwest Coast exhibit an early ancestral lineage and find that population structure existed among Native North American groups as early as the late Pleistocene.