Underthrusting of India below Eurasia has resulted in the formation of the Himalayan and the Qinghai–Tibet Plateau. Distributed deformation coupled with block translation and rotation has generated the Qilian Shan thrust belt and a series of east- and northwest-striking strike-slip faults across northeastern Tibet. Because these structures lie in a transition zone between the high plateau region to the south and the lowlands of the North China craton in the north, determining their deep-crustal and upper-mantle structures has important implications for unraveling the mechanism of Tibetan plateau formation. In this paper, we present new results from the SinoProbe-02 deep seismic reflection project across the eastern part of the Qilian Shan and the southern margin of the Alxa block. Interpretation of the reflection profile obtained from this study is based on constraints from surface geology and detailed geometric analysis of structural relationships among key reflectors in the crust and the upper mantle. Our results indicate that the upper crust of the eastern Qilian Shan is characterized by fault-bend folds and duplex systems involving Phanerozoic strata that may have resulted from early Paleozoic collisional tectonics and Cenozoic intra-continental deformation. Locally, half-graben structures hosting Cretaceous strata are also present. The active structures in the region are dominated by left-slip Haiyuan and Tianjian fault systems marking the northern margin of the Tibetan plateau. The strike-slip structures have variable dips and dip directions and sole into a common décollement with a depth of 40–45km. Because the two faults do not cut and offset the Moho below, the active crustal and mantle deformation in the northeastern Tibet must be decoupled.