The Northern Cordilleran slab window formed beneath western Canada concurrently with the opening of the Californian slab window beneath the southwestern United States, beginning in Late Oligocene–Miocene time. A database of 3530 analyses from Miocene–Holocene volcanoes along a 3500-km-long transect, from the northern Cascade Arc to the Aleutian Arc, was used to investigate mantle conditions in the Northern Cordilleran slab window. Using geochemical ratios sensitive to tectonic affinity, such as Nb/Zr, we show that typical volcanic arc compositions in the Cascade and Aleutian systems (derived from subduction-hydrated mantle) are separated by an extensive volcanic field with intraplate compositions (derived from relatively anhydrous mantle). This chemically defined region of intraplate volcanism is spatially coincident with a geophysical model of the Northern Cordilleran slab window. We suggest that opening of the slab window triggered upwelling of anhydrous mantle and displacement of the hydrous mantle wedge, which had developed during extensive early Cenozoic arc and backarc volcanism in western Canada. High heat flow throughout the western Canadian Cordillera is broadly coincident with the field of intraplate volcanism and is linked to slab window-induced mantle upwelling.