The Mackenzie Mountains (MMs) in the Yukon and Northwest Territories, Canada, are an enigmatic mountain range. They are currently uplifting (Leonard et al., 2008, https//doi.org/10.1029/2007JB005456), yet are about 700 km from the nearest plate boundary. Their arcuate shape is distinct and extends over 100 km eastward from the general trend of the Northern Canadian Cordillera. To better assess the cause and conditions of the current uplift, we processed ambient seismic noise data from a linear array of broadband seismographs crossing the mountains, along with other regional seismic stations, to estimate Rayleigh wave phase velocities between 6 and 40 s periods. From this, we estimated phase velocity dispersion and performed a tomographic inversion to estimate VS. Tomography reveals a low-velocity structure that extends upward from the base of the ∼50–66 km thick lithosphere to the upper crust, and we hypothesize that inferred low density and low rigidity associated with the VS anomaly localizes the ongoing uplift and thrust-dominated seismicity of the MMs. Additionally, we find relatively low crustal velocities that extend to the west of the MMs, suggesting that strain transfer from the Gulf of Alaska plate boundary plays a driving role as the crust translates to the northeast and buckles up against the craton consistent with the orogenic float hypothesis of Mazzotti and Hyndman (2002, https//doi.org/10.1130⁄0091-7613(2002)030〈0495:YCASTA〉2.0.CO;2). Finally, we observe lithospheric azimuthal anisotropy with an NW-SE fast direction. This is nearly orthogonal to teleseismic shear wave splitting measurements in the central MMs, and suggests that asthenosphere flow and lithospheric strain are not aligned in this region.