Lithospheric inheritance is thought to affect the location and reactivation of tectonic structures through successive cycles of supercontinent formation and dispersal; however, its relation to neotectonic activity remains unclear. In northwestern Canada, abundant seismicity throughout the northern Canadian Cordillera (NCC) is geographically confined by several crustal-scale boundaries, yet its southern extent terminates abruptly along the inferred westward extension of a Late Cretaceous rifted margin boundary called the Liard transfer zone (LTZ). We use seismic data to show that the uppermost mantle beneath the Cordillera exhibits a sharp north-south contrast in fabric across the LTZ. South of the LTZ, fast axes of seismic wave propagation align closely with the lithospheric mantle fabric orientation of the adjacent Canadian shield. North of the LTZ, fast axes are reoriented subparallel to the motion of the Pacific plate and follow the strike of the large dextral strike-slip Tintina and Denali faults. We attribute changes in anisotropic delay times across the Tintina and Denali faults to localized shear within the lithosphere; this implies that the crust and lithospheric mantle remained mechanically coupled during shearing. We propose that the contrast in uppermost mantle structure across the LTZ reflects a change in the nature and origin of the lithospheric mantle from inherited rifted margin structures, which affects the stability of the lithosphere and limits the extent of seismic activity within the NCC. These results indicate that neotectonic activity in modern Cordilleras is controlled in part by inherited upper mantle structures.