Uplifted rift margins are a common feature of continents and oceans. Two variants of rift flank morphologies have been recognized: One in which the topography warps down from an inland high toward the continental margin, and one where the tropographic peak lies close to the continental margin. The Great Escarpment of southern Africa and the Transantarctic Mountains are examples of the first and the second variants of rift flanks, respectively. Both rift flanks are bordered on their landward side by broad continental basins: the Kalahari and the Wilkes hinterland basins. If these basins are interpreted as flexural “outer lows” that deepen in unison with the uplift of the rift flanks, the lithosphere on the uplifted side is very rigid in both cases (elastic thickness T_e of 100 ± 20 km for southern Africa and 110 ± 20 km for East Antarctica). We suggest that the variation in rift flank morphology is caused by the isostatic response to uplift forces of elastic plates sharing different boundary conditions. We model the uplift of the Transantarctic Mountains as an upward deflection of an elastic plate which is broken at the front of the Transantarctic Mountains, and we model the uplift of the Great Escarpment as an upward deflection of a continuous elastic plate that is modified by the downward load of sediments on the continental margin. Although the Transantarctic Mountain uplift is young (60–0 Ma) and the southern African uplift is old (<100 Ma), the different isostatic responses of the two margins are not a function of age, because most loading (sedimentation) and unloading (erosion) took place shortly after rifting. Detailed modeling of topography, gravity, geological markers, and the locations of depocenters suggests that lithospheric rigidity decreases under the Transantarctic Mountains, whereas in southern Africa the decrease occurs not under the Great Escarpment but far seaward under the continental shelf and slope. If the distribution of lithospheric rigidity is indicative of the thermal regime of the lithosphere, then uplifted rift flanks are not always underlain by a thermal anomaly. This and other geological evidence indicate that a single mechanism cannot explain the uplift of both the Antarctic and the African margins.