Western China is a showcase of complex geological and geophysical features, including sedimentary basins, regimes of continental collisional tectonics, and the thickest crust found on earth. Here we present new results of a 2700-km-long seismic refraction profile across northwest China and the northeastern Tibetan Plateau. Seismic energy for this profile was provided by twelve chemical explosive shots fired in boreholes. The charge size ranged from 1500 to 4000 kg, sufficient to provide clear first arrivals to a maximum distance of 300 km. The distance between shotpoints ranged from 63 to 205 km, and the interval between portable seismographs was between 2 and 4 km. The profile was recorded along existing roads, and provided nearly straight profile segments. We have divided the seismic profile into two segments- the northern segment from the Altai mountains to the Altyn Tagh fault, and the southern segment from the Altyn Tagh fault to the Longmen Shan. The crustal velocity structure and Poisson’s ratio (s) for the transect, which provide a constraint on crustal composition, were determined from P- and S-wave data. The crustal thickness along the profile was determined, and the crust was found to have three layers with P-wave velocities (Vp) of 6.0-6.3 km/s, 6.3-6.6 km/s, and 6.9-7.0 km/s, respectively. We interpret the consistent three-layer stratification of the crust to indicate that the crust has undergone partial melting and differentiation after Paleozoic terrane accretion. Pn velocities were found to be ~7.7 to 7.8 km/s.