Although the Lhasa terrane of southern Tibet is an integral part of the Tibetan plateau, how the area has achieved its current high altitude of ~5000 m remains poorly understood. This is largely due to the fact that little is known about deep (>15 km) crustal structures and the depth and geometry of the Moho below the terrane. In this study, we address this question by acquiring and analyzing high-resolution seismic reflection data gathered from four high-energy dynamite shots along a 137-km north-south traverse spanning the southern Lhasa terrane. Our new seismic data reveal the presence of north-dipping reflectors in the crust, a seismically weak-reflection layer at the lowermost crust, and a sub-horizontal and locally discontinuous Moho at depth of 69–72 km with a crustal velocity of 6.30 km/s. The discordant relationship between the crustal dipping reflectors, the subhorizontal lower crustal layer, and the flat Moho suggests that the ~12-km basal section of the Lhasa terrane crust is a decoupling zone accommodating different styles of lithospheric-scale deformation. Because the north-dipping reflectors can be projected and/or connected with the reflectors in the Cenozoic Himalayan thrust system and the southernmost Lhasa terrane, we propose that the dipping crustal reflectors are parts of a south-directed crustal-scale thrust duplex created by the Cenozoic India-Asia collision. The relatively discontinuous and horizontal geometry at the base of the crust indicates that the Moho was reconstituted through ductile deformation in the lowermost crust caused by abnormally high temperature.