Predictions of 3-D crustal velocities driven by glacial isostatic adjustment (GIA) have generally been based on spherically symmetric Earth models. We adopt a finite-volume formulation to explore the impact of lateral variations in elastic plate strength, including lithospheric thickness changes across the continent-ocean interface and plate boundary weak zones, on these predictions. Weak zones introduce horizontal rate perturbations with a plate scale coherency and amplitudes reaching 1–2 mm/yr; radial velocity perturbations can be as large, but are geographically isolated to the weak zones (specifically, the North Atlantic Ridge). A discontinuity in ocean-continent lithospheric thickness significantly impacts rates along continental margins (order 1 mm/yr for radial rates and generally about half this for tangential rates). We conclude that lateral variations in lithospheric strength should be included in future GIA analyzes of space-geodetic survey results and in assessing the impact of GIA on the stability of geodetic reference frames.