High-resolution seismic reflection data from the West Kunlun Range front show that crustal structures beneath the northwestern margin of the Tibetan Plateau are dominated by nappes of upper crustal rocks. Geological cross-section balancing suggests an average of 24.6–54 km (38%–52%) of upper crustal shortening. This horizontal shortening by brittle folding and faulting in the upper crust correlates positively with crustal thickening, an increase in Moho depth by 5–7 km, and the topography. Our work suggests that upper crustal shortening is a chief factor for topographic uplift and crustal thickening at the northwestern margin of the Tibetan Plateau. Such a mechanism is different from that proposed for the plateau south of the Karakax strike-slip fault, where crustal flow may have played a prominent role in plateau uplift.