Portions of the bioregion fall within the traditional territories of the Lheidli T'enneh and Lhatako Dene First Nations; and the North Thompson, Soda Creek, Williams Lake, and Canim Lake Bands of the Secwepemc (Shuswap) First Nation. Though apparently not extensively populated at the time of first contact, a permanent Shuswap village existed at Tete Jaune and there was considerable seasonal use throughout the region.
Construction of the Grand Trunk Pacific and Canadian Northern Railways began settlement in earnest in the bioregion in the early part of the 20th century. Current communities are McBride, Valemount, Tete Jaune Cache, Dunster, Crescent Spur, Dome Creek, Penny, Longworth, Albreda and Blue River. The total population of the region is approximately 3,500.