Climate cooling during the late Cretaceous (ca. 100-66 Ma) has been linked to CO2 withdrawal due to enhanced denudation episodes recorded in the East-South American and West-South African margins. However, the onset of these episodes is recorded after the main cooling stage (i.e., Turonian-Santonian — ca. 93-83 Ma). Here, we investigate the clay fraction (< 2 μm) of sediments from the borehole O-A1 located in the continental slope of the Cape Basin, adjacent to the South African Margin. We combine these results with previous records from the basin (DSDP 361) to investigate the controlling factors in the denudation record along the South African Plateau and their relationship with the climate cooling during the late Cretaceous. The ΔεHf (proxy for silicate weathering intensity) record from site O-A1 shows an increase in silicate chemical weathering during the Cenomanian-Maastrichtian (ca. 95-68 Ma) interval, predating the Campanian-Danian interval shown by the DSDP 361 record, which offset to the site O-A1 is primarily linked to age model uncertainties from DSDP 361. This increase in silicate chemical weathering is concomitant to an enhanced phase of physical erosion and tectonic uplift of the South African Plateau as well as global climate cooling, suggesting this enhanced silicate chemical weathering phase is tectonically driven. Our ΔεHf(80) data from site O-A1 shows for the first time an increase in silicate chemical weathering as early as the Cenomanian, suggesting not only that it could have played a role maintaining the cool global climate trend during the late Cretaceous, but that this episode could have contributed to trigger the CO2 withdrawn responsible for this cooling that started by the Cenomanian-Turonian. Additionally, we suggest that this enhanced silicate chemical weathering episode along the South African Plateau might have influenced atmospheric CO2 concentrations and climate through two different mechanisms, initially via silicate reactions, but also through increased nutrient riverine input into the basin, which could have contributed to enhanced primary productivity and organic carbon storage as shown by the increase in Baexcess during the Santonian-Maastrichtian (ca. 85-65 Ma).