Rift-flank uplift adjacent to the Red Sea is asymmetric, i.e., a broad tilt of the entire Arabian plate along an axis parallel to the rift and more localized uplift on the African shoulder. A suite of models has been proposed to explain this pattern, but no model has considered the dynamic effects of large-scale mantle flow. Recent high-resolution images from seismic tomography show a massive, anomalously slow shear velocity structure that emerges from the core-mantle boundary beneath South Africa and that reaches close to the surface at the Red Sea. This buoyant megaplume has been identified as the driving mechanism for anomalously high topography in southern Africa and rifting in East Africa; in this paper we investigate its role in present-day African-Arabian topography. In particular, we present predictions of dynamic topography based on viscous-flow simulations initiated using seismically inferred mantle heterogeneity. These predictions demonstrate that viscous stresses associated with mantle flow are responsible for the long-wavelength signal in African-Arabian flank uplift. Our results do not preclude localized topographic contributions from other processes, particularly within the near field of the Red Sea.