Fast-axis directions obtained from shear-wave splitting analysis of core-refracted shear waves reveal several distinct anisotropic domains in the lower Great Lakes region. We used data from 27 broadband seismograph stations extending across a low-velocity anomaly in the lithospheric mantle. Observed splitting times vary from 0.4 to 1.4 s, with a mean of 0.7 s. A subset of the splitting vectors across a failed rift are oriented parallel to one arm of the rift zone; most others show a coherent pattern of fast directions close to the direction of plate motion, but oblique to surface tectonic belts. Within the area of the low-velocity anomaly, our observations are most simply explained by single-layer anisotropy induced by asthenospheric flow. Spatial variability in the direction and magnitude of splitting are consistent with a flow regime influenced by basal topology of the lithospheric keel.