Intrusive complexes with compositional diversity commonly document magma mixing processes and provide insights into regional magmatism and tectonics. Here, we present an integrated study involving detailed field investigations, petrography, mineral chemistry, whole-rock geochemistry, SrNd isotopic compositions, and zircon U–Pb–Hf isotopes for the Quxu intrusive complex in southern Tibet, with the aim of constraining the origin of the complex and gaining insights into the early Eocene magmatism and geodynamics of the southern Lhasa subterrane. The Quxu intrusive complex consists predominantly of tonalites and minor pyroxene–hornblende gabbronorites, with lesser amounts of quartz diorites within the contact zones of these two types of rock. Zircon LA–ICP–MS UPb dating yields crystallization ages of ~51 Ma for all lithologies in this complex. The pyroxene–hornblende gabbronorites show replacement of pyroxene by amphibole and/or biotite and contain plagioclase crystals of variable composition (An38–74) and quartz, characteristics that are consistent with a reactive process via magma mixing. The quartz diorites and tonalites preserve plagioclase crystals with complex oscillatory zoning and repeated resorption surfaces, indicating a magma mixing origin. Geochemically, the pyroxene–hornblende gabbronorites, quartz diorites, and tonalites exhibit continuous variations in most of their major- and trace-element compositions, consistent with published data for mafic microgranular enclaves (MMEs) and host granitoids that resulted from magma mixing. All the lithologies in the Quxu intrusive complex have homogeneous and depleted isotopic compositions, with whole-rock initial 87Sr/86Sr ratios (ISr) of 0.7038–0.7041, εNd(t) values of +5.5 to +6.3, and zircon εHf(t) values of +8.5 to +12.9. These geochemical and isotopic data, combined with the mineralogical features, indicate that the Quxu intrusive complex originated from magma mixing between mafic and felsic end-members in varying proportions. The mafic end-member was derived from the decompression melting of upwelling asthenosphere, and the felsic end-member was derived from the partial melting of juvenile lower crust triggered by underplating of a mafic end-member. Our results also indicate that breakoff of the Neo-Tethyan oceanic slab was responsible for the generation of the Quxu intrusive complex and, more generally, for the early Eocene magmatism in the southern Lhasa subterrane.