Surface uplift occurs as a result of tectonic uplift related to crustal deformation and isostatic compensation due to surface erosion. To determine and quantify the key controlling factors responsible for surface uplift in the south‐eastern Tibetan Plateau, we calculated isostatic compensation using topographic data along five wide‐angle seismic profiles across the Chuandian Block, Indochina Block, and South China Plate, and examined the correlations between tectonic uplift and each crustal layer thickness. The average isostatic compensation caused by surface erosion is 340–480 m, which is approximately 13–26% of the total surface uplift. The geodynamic implications in relation to the Global Positioning System, focal mechanisms (P axes), seismic anisotropy (Pms splitting), and low‐velocity zones were also investigated. The low‐velocity zones with long‐distance southward extension seemed to be significantly reduced, and were divided into two branches by resistance from the inner zone of the Emeishan large igneous province (ELIP) when it is extending into the southern Chuandian Block. The lower crustal thickening related to low‐velocity zones reconstructed a partial crustal structure of the ELIP, and contributed at least 53–62% of the total surface uplift at the western branch, and almost 46–65% at the eastern branch. With the limitations imposed by the rigidity of the South China Plate and Indochina Block, the south‐eastern motion of the upper‐middle crust was strongly decoupled with southward lower crustal flow, as revealed by the unmatched pattern between P axes and Pms splitting. The south‐eastward motion of southern Chuandian Block resulted in upper‐crustal folding in the W–E direction, upper‐crustal thrusting in the N–S direction, and contributed approximately 9–28% of the total surface uplift in some locations. We emphasize the indispensability of upper‐crustal shortening in the frontal zone of the south‐eastern Tibetan Plateau and introduce the transitional characteristics of the southern Chuandian Block, from typical lower crustal flow to coupled crustal brittle shortening.