Source-to-sink research has often used sediment fluxes as a fundamental parameter when seeking to understand the perturbations caused by tectonics or climate. This parameter is often interpreted only in terms of erosion rates, dismissing the component exerted by chemical weathering. In this study, we characterize sediments from the Deep Surface Drilling Program core 361 (DSDP 361) located in the Cape basin to show the evolution of both, physical erosion and silicate chemical weathering, during the late Cretaceous (100.5–66 Ma) in the source-to-sink system consisting of the South African plateau and the Cape Basin. TEM images and trace element analyses indicate that detrital clays predominate within the site and thus reflect variations in surface continental processes. Clay mineralogy shows a predominance of detrital smectite (60–98%) throughout the section. However, an increase in primary clay minerals, in particular illite (20%), indicates a relative enhancement in physical erosion, while an increase in palygorskite (10%) indicates regional climate aridification during the Campanian–Danian interval (ca. 77–62 Ma). Concomitant to this enhancement, we observe both, more radiogenic Hf isotopic compositions and less radiogenic Nd isotopic compositions in the clay fractions (< 2 μm). These variations can be respectively associated to an increase in silicate chemical weathering and the incorporation of unradiogenic material, likely related to the orogenic belts present on the western-south margin of Southern Africa. The regional aridification and the global climate cooling trend observed in δ18O benthic foraminifera records do not appear as suitable mechanisms for the increase in physical erosion and silicate chemical weathering observed. Our results, together with the reported increase in sedimentation rates and the reported tectonic uplift between 80 and 70 Ma, suggest that it is tectonic activity and not climate the main driver in the enhancement of denudation processes. Furthermore, our data suggests that such uplift episode could have impacted the regional climate by causing a rain-shadow effect, with an inland aridification suggested by the increase in palygorskite proportions. The increase in silicate weathering suggested by our new dataset begins in the Campanian (ca. 77 Ma), later than the onset of the global climatic cooling trend that occurs from the Turonian onward. If enhanced weathering of the South African Plateau may not have triggered the recorded climatic cooling, it may have contributed to maintain cooler conditions in the Campanian-Danian interval.