The timing and causes of the >1.0 km elevation gain of the southern African Plateau since Paleozoic time are widely debated. We report the first apatite and titanite (U-Th)/He thermochronometry data for southern Africa to resolve the unroofing history across a classic portion of the major escarpment that encircles the plateau. The study area encompasses ∼1500 m of relief within Archean basement of the Barberton Greenstone Belt region of the eastern Kaapvaal craton. Titanite dates are Neoproterozoic. Apatite dates are Cretaceous, with most results clustering at ca. 100 Ma. Thermal history simulations confirm Mesozoic heating followed by accelerated cooling in mid- to Late Cretaceous time. The lower temperature sensitivity of the apatite (U-Th)/He method relative to previous thermochronometry in southern Africa allows tighter constraints on the Cenozoic thermal history than past work. The data limit Cenozoic temperatures east of the escarpment to ≤35 °C, and appear best explained by temperatures within a few degrees of the modern surface temperature. These results restrict Cenozoic unroofing to less than ∼850 m, and permit negligible erosion since the Cretaceous. If substantial uplift of the southern African Plateau occurred in the Cenozoic as advocated by some workers, then it was not responsible for the majority of post-Paleozoic unroofing across the eastern escarpment. Significant Mesozoic unroofing is coincident with large igneous province activity, kimberlite magmatism, and continental rifting within and along the margins of southern Africa, compatible with a phase of plateau elevation gain due to mantle buoyancy sources associated with these events.