The continuous collision and convergence of the Indian and the Eurasian plates initiated during the early Cenozoic resulted in large-scale intra-continental deformation within the Eurasian plate. This event reactivated the Tian Shan orogenic belts, which propagated the thrust toward the Tarim basin, forming the present southern Tian Shan fold-thrust belts with significant spatial variation in deformation along the strike of the belts. In this paper, we analyze the spatial variation of deformation and its possible controlling factors based on the seismic profile interpretation and balanced cross-sections across the structural belts. This study suggests that the western segment of the southern Tian Shan fold-thrust belts can be subdivided into the Bashibu lake segment, the Wuqia-Atushi-Kashi segment, and the west Keping segment. Among them, a series of double-thrust structures and back-load basins were mainly developed in the Bashibu lake tectonic segment. The deformation characteristics of the Wuqia-Atushi-Kashi tectonic section were manifested in two levels: stacking structure and tectonic wedge developed in the deep part, and fault-propagating folds and fold belts reconstructed by southward thrust faults developed in the shallow part. The deformation of west Keping was more intense and also manifested in two levels: stacking structure developed in the deep part, fault-propagating folds, fold belts reconstructed by southward thrust faults and recoiling structural system developed in the shallow part. Based on the geology of the study area, it is concluded that the strata deformation variation in the western section of the southern Tian Shan fold-thrust belts may be related to the northward advance of the Pamir block since the Cenozoic era, the activity of the Taras-Fergana right strike-slip fault, the influence of the activation of preexisting faults and ductile slippage.