The Lhasa terrane in southern Tibet occupies a central position in Asian tectonics, yet its pre‐Mesozoic petrologic and tectonic evolution is poorly constrained, especially the Southern Lhasa subterrane (SLS). Here, new zircon U–Pb ages, zircon trace element and Hf isotopic compositions, and whole‐rock geochemical data for mafic meta‐igneous rocks from the SLS distinguish three tectono‐thermal events at ∼290 Ma, ∼126 Ma and ∼49 Ma. Whole‐rocks and zircons with ages of the two older events have arc magma geochemistry, but Hf isotopes are distinct from Mesozoic Gangdese arc magmas. Zircon cores and, arguably, whole rocks instead derive from ∼290 Ma magma formed during southward subduction of Paleo‐Tethys beneath the SLS. These rocks later underwent Early Cretaceous (∼126 Ma) remelting and early Cenozoic (∼49 Ma) metamorphism with P–T conditions of ~800°C and 15.3 kbar, and record a retrograde P–T path characterized by exhumation with cooling, consistent with a collisional origin. These data suggest Permian igneous rocks underwent reworking during both the Early Cretaceous and the early Cenozoic, reaching crustal thicknesses of at least ~50 km during the early Eocene. Combined with regional data, Paleo‐Tethys evidently experienced early Permian double‐sided subduction within the Lhasa terrane, with back arc basins forming between the SLS and the Indian margin to the south. These back arc basins ultimately widened to form the Neo‐Tethys Ocean, which then subducted during the Mesozoic, leading to Cretaceous arc magmatism and overprinting, followed by early Cenozoic metamorphism and final reworking during collision with India.