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The petrogenesis and tectonic evolution of the Mesozoic ophiolitic melanges in the western section of the Yarlung Zangbo suture zone (YZSZ) remain controversial. In this paper, we present the results of whole-rock geochemical and Sr Nd isotope analyses, zircon U Pb ages and in situ Lu Hf isotopic data obtained from mafic rocks of the northern and southern sub-belts of the western YZSZ Mesozoic ophiolitic melanges to help us understand these controversial issues. Diabases and dolerites from the northern sub-belt and gabbros from the southern sub-belt exhibit variable fore-arc basalt (FAB)-like geochemical compositions and have zircon U Pb ages of ∼126.4–120.3 Ma. In addition, gabbro-diabases from the northern sub-belt have boninite series affinities and yield a zircon U Pb age of ∼125.7 Ma. These results, along with previous studies on the YZSZ Mesozoic ophiolitic melanges and the Gangdese arc, reveal that the western YZSZ Mesozoic ophiolites were likely generated over multiple stages in the epicontinental Gangdese fore-arc basin as the Yarlung Zangbo Neo-Tethyan Ocean subducted northward in front of the Lhasa terrane. The Early Cretaceous FAB-like and boninite series mafic rocks were formed by the reinitiation of subduction, which was followed by a retreat of the subduction zone and the creation of the fore-arc basin and strong hyperextension, accompanied by asthenosphere upwelling at ∼130–120 Ma. During this process, the upwelling asthenosphere underwent decompressional melting with limited penetration of slab-derived fluids and gave rise to the N-MORB (normal mid-ocean ridge basalt)-like basaltic magmas that intruded the overlying, previously generated depleted mantle as FAB-like gabbro, diabase and dolerite sills or dykes. Then, boninitic magmas represented by boninitic gabbro-diabases were generated by remelting the extremely depleted residual mantle source, which was metasomatized by a small amount of slab-derived fluids, following previous extractions of FAB-like magma.