Porphyry systems, the most important reserves of Cu and Mo with significant Au, are genetically linked to the emplacement of hydrous and oxidized intermediate to acidic magmas, in response to temporal and geochemical evolution of crust in orogenic terranes. In this study, comprehensive whole-rock and zircon geochemical and isotopic datasets of intermediate to acid igneous rocks were integrated to characterize the crustal evolution and metallogeny of porphyry deposits in the Central Asian Orogenic Belt (CAOB). The ore-forming porphyries of Cu ± Au ± Mo and Mo deposits have higher but largely overlapped ΔFMQ (the proxy for oxygen fugacity) with those of the barren igneous rocks. However, the ore-forming porphyries of Cu ± Au ± Mo deposits are characterized by distinctly higher whole-rock V/Sc and zircon Eu/Eu∗ (both are proxies for water content) than barren rocks. Furthermore, the V/Sc ratios positively correlate with the Cu tonnages of calc-alkali porphyry Cu deposits, suggesting that magmatic water contents may yield the first-order control on metal endowment. The general decrease of V/Sc from the Paleozoic to Mesozoic, combined with the negative correlation of V/Sc with K2O and SiO2, also indicates the gradual evolution of crust in CAOB clearly controls the end members of porphyry-type systems (i.e., Cu‒>Au and Mo deposits). The crustal residence age (TRes, the time difference between Nd depleted-mantle model age and the crystallization age) of c. 500 Ma from the Nd isotopes is proposed as the threshold distinguishing porphyry Cu ± Au ± Mo (TRes < 500 Ma) and Mo deposits (TRes > 500 Ma) in the CAOB. The coupled zircon Hf isotopes and crustal thickness reveal that the fundamental crustal architecture in the eastern and western CAOB had been built by the Late Permian and Late Carboniferous, respectively, highlighted by the converging trends of ϵHf(t) commencing at c.250 Ma in the eastern segment and c.300 Ma in the western segment of CAOB, indicating reworking and homogenizing of juvenile crust after collision. In the eastern CAOB, porphyry Cu ± Au ± Mo deposits were formed by juvenile materials in thin island arcs, while porphyry Mo deposits were formed by reworked materials in the thickened orogenic crust after c.250 Ma. In the western CAOB, porphyry Cu deposits in the Balkhash region during the Late Carboniferous were formed in thickened continental crust (generally > 40 km), genetically linked to the culmination of world-wide magmatic addition rates (MARs) triggered by accelerated production of the juvenile crust, in contrast to the porphyry Cu ± Au ± Mo deposits formed in thin island arc (generally < 40 km) during the Early Paleozoic. This study tests the zircon ΔFMQ as proxy for fO2, and zircon Eu/Eu∗ and whole-rock V/Sc ratios as proxy for water content. It highlights that whole-rock V/Sc ratio is a favorable index for the Cu tonnages of porphyry Cu ± Au ± Mo deposits, and that the distinct porphyry-type mineralization in the CAOB is controlled by the crustal evolution reflected by crustal composition and thickness.