The most striking structural features in the interior of the Shan Plateau, southeast of the eastern Himalayan syntaxis, are a series of NE-trending faults that exhibit sinistral movement and an arcuate geometry. Their origin and tectonic evolution remain poorly understood. Furthermore, a switch in slip sense is recorded along many of these faults, but the timing of kinematic reversal is still unclear, hindering an understanding of the causal geodynamic mechanisms. We conducted an integrative study of apatite and zircon (U-Th)/He thermochronology, 40Ar/39Ar geochronology, and structural and geomorphic analysis to decipher the evolution of two major NE-trending faults: the Nantinghe and Dayingjiang faults. At least three deformation stages are identified within the Nantinghe fault zone, including top-to-the-SE/ESE thrusting, dextral ductile strike-slip shearing, and sinistral movement. Zircon and apatite (U-Th)/He data, collected from the northeastern terminus of the Nantinghe fault, reveal rapid cooling in the early Miocene. Combined with the 40Ar/39Ar data from sinistrally sheared mylonite, left-lateral movement on the Nantinghe fault is inferred to have initiated as early as ca. 20 Ma. The Dayingjiang fault reactivated as a sinistral brittle fault along the dextral Yingjiang shear zone. A two-stage thermal history is identified along the shear zone, with prominent cooling during dextral ductile shearing in the early- to mid-Miocene followed by a lower-magnitude cooling episode at ca. 11 Ma caused by sinistral transtension along the Dayingjiang fault. The evolution of the Nantinghe and Dayingjiang faults suggests that the NE-trending fault system in the Shan Plateau may have developed along preexisting structures and underwent diachronous slip-sense inversion in the late Cenozoic. The northward advance of the eastern Himalayan syntaxis caused a major change in both the regional stress field and fault geometries in the eastern India-Eurasia oblique convergence zone, contributing to the inversion of fault kinematics.