The Tarim basin in NW China developed as a complex foreland basin in the Cenozoic in association with mountain building in the Tibetan Plateau to the south and the Tian Shan orogen to the north. We reconstructed the Cenozoic deformation history of the Tarim basement by backstripping the sedimentary rocks. Two-dimensional and three-dimensional finite element models are then used to simulate the flexural deformation of the Tarim basement in response to the sedimentary loads and additional tectonic loads associated with overthrusting of the surrounding mountain belts. The results suggest that uplift of both the western Kunlun Shan and the Tian Shan orogens started during or before Oligocene. Since the Miocene, mountain building accelerated in the western Kunlun Shan but showed segmented development in the Tian Shan. The results also indicate reduced tectonic load along the Altyn Tagh fault since late Miocene, consistent with geological and geophysical evidence of the fault cutting the entire lithosphere and migrating southward during its cause of the Cenozoic evolution.