The Lhasa Terrane in southern Tibet is the leading edge of the Tibet-Himalaya Orogen and represents a fragmentary record of terminal oceanic subduction. Thus, it is an ideal region for studying magmatism and geodynamic processes that occurred during the transition from oceanic subduction to continental collision and/or oceanic slab breakoff. Here we examine a suite of early Cenozoic mafic rocks (ca. 57 Ma) within the central part of Lhasa Terrane, southern Tibet, which erupted during a transitional phase between the onset of India-Asia continental collision and Neo-Tethyan slab breakoff. These rocks display a geochemical affinity with magmas produced by fluid-fluxed melting of the mantle wedge within a subduction zone environment. The whole-rock element and Sr-Nd isotope compositions of these mafic rocks are similar to those of Cretaceous subduction-related magmatism in southern Tibet, demonstrating the sustained influence of the Neo-Tethys Ocean slab on the mantle wedge during the onset of the collision of India and Asia. The results of our geochemical forward modeling constrain the conditions of melt generation at depths of 1.3−1.5 GPa with significant fluid additions from the Neo-Tethyan slab. These results provide the first petrological and geochemical evidence that slab flux-related magmatism continued despite the commencement of continental collision. While existing studies have suggested that magmas were derived from melting of the Neo-Tethyan slab during this period, our new results suggest that additional magma generation mechanisms were active during this transitional phase.