We present a new crust and upper mantle cross section of the western India-Eurasia collision zone by combining geological, geophysical, and petrological information within a self-consistent thermodynamic framework. We characterize the upper mantle structure down to 410 km depth from the thermal, compositional, and seismological viewpoints along a profile crossing western Himalayan orogen and Tibetan Plateau, Tarim Basin, Tian Shan, and Junggar Basin, ending in the Chinese Altai Range. Our results show that the Moho deepens from the Himalayan foreland basin (~40 km depth) to the Kunlun Shan (~90 km depth), and it shallows to less than 50 km beneath the Tarim Basin. Crustal thickness between the Tian Shan and Altai mountains varies from ~66 km to ~62 km. The depth of the lithosphere-asthenosphere boundary (LAB) increases from 230 km below the Himalayan foreland basin to 295 km below the Kunlun Shan. To NE the LAB shallows to ~230 km below the Tarim Basin and increases again to ~260 km below Tian Shan and Junggar region and to ~280 km below the Altai Range. Lateral variations of the seismic anomalies are compatible with variations in the lithospheric mantle composition retrieved from global petrological data. We also model a preexisting profile in the eastern India-Eurasia collision zone and discuss the along-strike variations of the lithospheric structure. We confirm the presence of a noticeable lithospheric mantle thinning below the Eastern Tibetan Plateau, with the LAB located at 140 km depth, and of mantle compositional differences between the Tibetan Plateau and the northern domains of Qilian Shan, Qaidam Basin, and North China.