Compared with the Mesozoic W–Sn–Cu–Au (Pb–Zn–Ag) mineralization in the South China Mo Province (SCMP), detailed studies on Mo deposits, especially Cretaceous Mo deposits are rare due to limited exposures. The Sanzhishu porphyry Mo deposit, located in the SCMP, is characterized by disseminated and veinlet-type molybdenite–quartz veins within monzogranite. Zircon SIMS U–Pb analysis of the monzogranite yields a concordia age of 112.3 Ma, indicating that the emplacement of the Sanzhishu monzogranite was in the Early Cretaceous. Six molybdenite samples yield Re–Os ages between 111 and 112 Ma, with an isochron age of 111 ± 6.4 Ma, which is consistent with the zircon age of the ore-bearing monzogranite. A new compilation of reliable Re–Os isotope age data indicate that Cretaceous Mo mineralization in the SCMP, occurred during two major episodes at 130–145 Ma and 90–120 Ma, with most deposits forming in the later episode. During the Cretaceous, a back-arc extensional setting in SE China is evidenced by the occurrence of numerous high-F Mo deposits, widespread A-type granites and the development of pull-apart basins. The increasing trend in Re contents of molybdenite from the early Mo mineralization period to the late Mo mineralization period in the SCMP indicates that the area experienced stronger crust–mantle interaction in the later mineralization episode. Based on geological evidence, we propose that the early episode of Mo mineralization formed in a tectonic setting associated with a metamorphosed subducted slab that experienced an increase in density and an increase in the gravitational pull on the slab itself, which induced rollback of the subducting Paleo-Pacific slab. The late episode of Mo mineralization developed in an extensional tectonic setting caused by the continued rollback and the eventual slab break-off.