The Gangdese batholith, more than 2500 km in length, is composed mainly of Jurassic-Miocene igneous rocks. This batholith is one of the most important constituents of the Tibetan orogenesis and provides an ideal place for study of Neo-Tethyan ocean geodynamic evolution and plateau uplift. Recent studies on the Gangdese Jurassic felsic magmatism highlight its juvenile source. However, important aspects concerning the genesis of the juvenile magmatism and related deep geodynamic evolution are still unclear. Here, we report detailed petrological, geochronological, geochemical, whole-rock Sr-Nd isotopic, and in situ Sr-Hf isotopic data for a recently identified hornblende gabbro in the Dongga area, southern Lhasa sub-block. This hornblende gabbro is dominated by hornblende and plagioclase, dated at Early Jurassic (ca. 180–190 Ma), and characterized by a narrow compositional range in SiO2 (49.38wt%–52.27wt%), MgO (4.08wt%–7.00wt%), FeO (10.43wt%–11.77wt%), Na2O (2.58wt%–3.51wt%), and K2O (0.48wt%–1.53wt%). It has depleted isotopic signatures, with whole-rock (87Sr/86Sr)i ratios of 0.7033–0.7043, εNd(t) values of +4.90 to +6.99, in situ plagioclase (87Sr/86Sr)i ratios of 0.7034–0.7042, and zircon εHf(t) of +12.2 to +16.8. Our results integrated with published data suggest a model of Gangdese juvenile crustal growth by a subduction-related water-enriched mantle wedge. The hydrous partial melting of the lithosphere mantle was triggered by the dehydration of a Neo-Tethyan oceanic slab. This mafic magmatism emplaced in the middle-lower crust of intraoceanic arcs or active continental margins, leading to Jurassic juvenile crustal growth in southern Tibet.