Although the Indus-Tsangpo Suture (ITS) is the most spectacular thrust system of continent-continent collision in the world, fundamental questions about its strength evolution and deformation behavior transition remain unanswered. Here we reported, for the first time, frictional melting-induced pseudotachylytes in the intensively deformed felsic rocks along the ITS zone in southern Tibet. This study reveals that pseudotachylytes induced profound weakness of the boundary fault between Indian and Asian plates. The intrinsically low strength of the foliated microlites crystallized from frictional melt or glass (i.e., pseudotachylyte) at seismogenic depths compared with the surrounding coarse-grained quartzofeldspathic rocks in the brittle and semi-brittle regime is sufficient to explain the localization of shear strain, the development of ductile shear zones embedded in strong wall rocks, and the transition from the strong to weak fault behaviors without invoking the presence of high fluid pressure or low friction coefficient metasomatic materials (e.g., smectite or lizardite) within the faults.