Compared to other Mo provinces, few studies focused on the South China Mo Province (SCMP), especially for Early Cretaceous Mo mineralization. The Lufeng porphyry Mo deposit in the SCMP is characterized by disseminated and veinlet-type mineralization in granite porphyry, gneiss, and rhyolite. In this study, six molybdenite samples yield a Re–Os isochron age of 108.0±1.8 Ma, which is consistent with the zircon U–Pb age of the granite porphyry (108.4±0.8 Ma). The coincidence of magmatic and hydrothermal activities indicates that Mo mineralization was associated with the intrusion of granite porphyry during the late Early Cretaceous. A compilation of U–Pb and Re–Os chronological data suggests that an extensive and intensive Mo mineralization event occurred in the SCMP during the late Early Cretaceous. The marked difference in molybdenite Re contents between Cu-bearing (85–536 ppm) and Cu-barren (1.3–59 ppm) Mo deposits of the late Early Cretaceous indicates that the ore-forming materials were derived from strong crust–mantle interactions. Together with regional petrological and geochemical data, this study suggests that late Early Cretaceous Mo mineralization in the SCMP occurred in an extensional setting associated with the roll-back of the Paleo-Pacific slab.