Molybdenite-bearing porphyry deposits are the predominant supplier of molybdenum to industrialized society and one of the main hosts of Mo in the upper continental crust. The Mo isotope compositions (δ98/95Mo, normalized to NIST3134 equals 0‰) of molybdenite show considerable variation (–1.62 to +2.27‰), but the factors controlling this variability remain poorly constrained. This information is critical for underpinning genetic models of porphyry deposits, understanding elemental cycling, and utilizing the δ98/95Mo of marine sediments as a paleoredox proxy. Using the well-characterized Qulong porphyry Cu-Mo deposit (Tibet) as an example, here we discuss how rapid cooling, facilitated by mixing hot magmatic fluid with cold meteoric water, can be a controlling factor on efficient mineralization, and then tackle how fluid evolution regulates molybdenum isotope fractionation. Molybdenites, which preferentially partition isotopically light Mo (Rayleigh fractionation), precipitated from a single fluid will develop a heavier δ98/95Mo composition over time, and this also creates heterogeneous δ98/95Mo between molybdenite grains. Whereas a fluid undergoing multiple episodes of intensive boiling will gradually lose its isotopically heavy Mo to the vapor phase, molybdenites crystallizing successively from the residual liquid will then have lighter δ98/95Mo over time. However, when mineralization efficiency becomes too low, a negligible variation in δ98/95Mo of molybdenite is observed. Given that the mineralization efficiency (i.e., the amount of Mo crystallized as molybdenite from the fluid) rarely reaches 100% and molybdenite favors isotopically light Mo, the presence of a residual fluid with isotopically heavy Mo is inevitable. This residual fluid may then become trapped in alteration halos; hence, δ98/95Mo has the potential to aid in locating the mineralization center (e.g., lighter δ98/95Mo toward the orebody). The residual fluid may also feed surface hydrological systems and eventually impact Mo cycling. Our study highlights that understanding the controls of isotope fractionation is critical to bridge the gap between ore formation and elemental cycling, and that other transition metals (e.g., Cu, Fe, and Zn) may follow similar trajectories.