—The Qilian Shan (or Qilian Mountains), located on the northeastern margin of the Tibetan Plateau, is an actively growing orogenic belt resulting from the far-field impact of the India–Eurasia collision. The northward penetration of the Indian Plate is responsible for intense crustal shortening in the Qilian Shan. However, the tectonic deformation pattern in response to the crustal shortening remains unclear. In this study, we present the regional seismicity, fault activity, and GPS crustal movement velocity field to characterize the active tectonic deformation of the Qilian Shan based on historical data over the past two decades. The results suggest that the western Qilian Shan is characterized by distributed north–south crustal shortening, while the eastern Qilian Shan is dominated by blocklike eastward extrusion of crust along major strike-slip faults coupled with clockwise rotation. North–south crustal shortening and east–west lateral extrusion, two deformation modes responding to the India–Eurasia convergence, match the crustal deformation in the Qilian Shan. The tectonic deformation of the western Qilian Shan is largely in agreement with the former, while the eastern Qilian Shan corresponds closely to the latter. Lower crustal flow beneath the central Tibetan Plateau provides the potential driving force to induce the eastward extrusion of crustal material out of the plateau and the growth of some boundary mountain ranges, such as the Qilian Shan.