The Central Yunnan Plateau (CYP) is located in the southeastern end of the Sichuan-Yunnan rhombic block. CYP is surrounded by the South China Block to the east and the Indo-China Block to the southwest. Stratigraphy and topography research shows the relative surface uplift of the CYP since the Pliocene. However, the widely accepted model of lower crustal flow is very difficult to fully explain the surface uplift of CYP, with faults and fold structures in the brittle shallow crust. The lower crust thickening led by the lower crustal flow only contributes 34–54% (600–950 m) of the total surface uplift. The wide-angle seismic profiles and topography analysis show that the CYP surface uplift is predominately a consequence of isostatic compensation due to surface erosion, upper-middle crustal shortening, and lower crustal thickening. The average isostatic adjustment caused by surface erosion of CYP is about 500 m, which is about 29% of the total surface uplift (1750 m). The GPS station velocities, focal mechanisms, and seismic anisotropy show the strong decoupling relationship between upper-middle crust and lower crust. In detail, there is a movement with southeast-directed and clockwise rotation around the Eastern Himalayan syntaxis in the upper-middle crust, although south-directed flow in the lower crust. The southeast motion of the upper-middle crust could be resolved into two portions. The eastward component of upper-middle crust motion is obstructed by the South China Block in the east. The result is the W-E direction shortening of upper-middle crust, shown by the S-N trending CYP anticlinorium. The W-E direction shortening of upper-middle crust contributes 17–37% (300–650 m) of the total surface uplift. In contrast, the southward component of upper-middle crust motion, shown by the sinistral strike-slip displacement of the Xiaojiang fault zone, could pass through the Red River fault zone into the Indo-China Block, where the left-lateral Dien Bien Phu Fault would be the counterpart. The contribution of upper-middle crustal shortening in a S-N direction is very limited. The lower crustal flow could have been playing a prominent role in the growth of the whole southeast margin of the Tibetan Plateau, and the contribution from upper-middle crustal shortening cannot be ignored in some local areas.