Pleistocene weathering, uplift rates, and mass movements have been studied and correlated in a key-area of the Italian southern Apennines. The study area is the Melandro River valley, developed in a tectonically-controlled Quaternary intermontane basin of the axial zone of the chain. The goal of this paper is to assess ages and geomorphic features of two paleo-landslides and to relate them to values of uplift rates and the climate conditions in the axial zone of the chain during the Pleistocene. Uplift rates have been estimated using elevation and age of flat erosional land surfaces. In the southern area of the basin, the landscape features a wide paleo-landslide which can be ascribed to the upper part of the Lower Pleistocene on the basis of relationships with Quaternary deposits and land surfaces. Another paleo-landslide, in the northern sector of the basin, can be referred to the beginning of the Upper Pleistocene. The correlation between the ages of the two landslides and the temporal trend of the uplift rates allowed us to hypothesize that mass movements occurred in response to uplift peaks that destabilized slopes. Additionally, deciphering weathering conditions by means of the analysis of mineralogical and geochemical signals from landslide deposits and weathered horizons allowed assessment of changes in paleoclimate scenarios during the Pleistocene. The deep weathering was probably caused by the onset of warm-humid climate conditions, which may have acted as a further factor triggering landslide movements in an area already destabilized by the rapid uplift.