The arch-and-basin geometry that characterizes North Africa was achieved at the end of Paleozoic times. It has been subsequently reactivated during the Mesozoic-Cenozoic with, in particular, the development of large topographic anomalies. Among these, the Tuareg Shield forms a topographic high in which the Pan-African basement reaches 2400 m above sea level (Hoggar core). While Cretaceous sedimentary remnants suggest a possible stage of subsidence during the Mesozoic, currently the area forms a swell, emphasized by Cenozoic volcanic episodes since 35 Ma. In this context, we present the first apatite (U-Th)/He thermochronological data acquired across this swell, with mean ages ranging from 78 ± 22 Ma to 13 ± 3 Ma. These results demonstrate the existence of a widespread Eocene exhumation of the shield before volcanic activity began, which reflects large-scale vertical processes. In the northeastern part of the swell, Cretaceous continental sedimentary remnants unconformably lying on the basement close to our samples evidence that they were near the surface at that time. This study shows that basement rocks have undergone subsequent heating at ∼60–80 °C, suggesting a burial of more than 1 km after the Early Cretaceous. This conclusion can be possibly extended over the whole Tuareg Shield.