Cu-Mo deposits are commonly associated with calc-alkaline porphyries and derived from subduction-modified lithosphere in magmatic arcs. Here we report the Wangjiazhuang Cu-Mo deposit, which is peculiarly associated with an alkaline quartz monzonite that originated from a metasomatized asthenospheric mantle within an intracontinental setting in the eastern North China Craton (NCC). The deposit was formed at ca. 128.3 ± 0.7 Ma (2σ), basically coincident with the emplacement of the host quartz monzonite (128.8 ± 1.0 Ma, 2σ). Pegmatitic vein-type and stockwork-/disseminated-type mineralizations were identified in the deposit, of which the former is shallowly situated and characterized by coarse and well-crystallized Cu- and Mo-bearing sulfides + quartz + biotite + K-feldspar assemblages, whereas the latter is deeply situated and characterized by stockworks or Cu- and Mo-bearing sulfides disseminated in the altered quartz monzonite. Separation between Cu-rich and Morich ore bodies at shallow depth was also observed. The Cu-Mo mineralization is typically associated with potassic-silicic alteration. High-temperature fluid inclusions with halite/sylvite daughter minerals (having homogenization temperatures of 287–466 °C and salinities of 33.8–55.3 wt% NaCl equivalent) suggest a magmatic origin of the ore-forming fluids. Differentiation of the fluids into vapor-rich and liquid-rich phases occurred during the magmatic-hydrothermal processes, as indicated by the coexistence of vapor-rich, liquid-rich and daughter mineral-rich fluid inclusions with similar homogenization temperatures. LA-ICP-MS analysis of the fluid inclusions shows that Cu is highly partitioned into the vapor-rich fluid inclusions, whereas Mo is mainly concentrated in the daughter mineral-rich fluid inclusions. This implies that phase differentiation of the oreforming fluids was likely responsible for the separation of Cu-rich and Mo-rich ore bodies. The presence of hematite in the fluid inclusions also suggests high oxidation state of the ore-forming fluids. Based on the variations of δ34S in sulfides and Al contents in quartz, continuous reduction of the oxidized ore-forming fluids, coupled with pH change of the fluids during water-rock interaction, led to the deposition of the ore-forming metals. The host quartz monzonite shows adakitic geochemical signatures. Fractional crystallization of low-Mg amphiboles contributed to the adakitic signatures. According to the mixing modeling using Sr-Nd isotopes, the quartz monzonite was mainly derived from asthenospheric mantle-derived magma mixed by ∼15–20% lower crust components at the base of the lower crust. Zircon saturation thermometry and Ti-in-quartz thermobarometer suggest that the rock was emplaced at the temperature of ∼746 °C and the depth of ∼4 km. High water (H2O ≥ 4 wt%) and metal (Cu is up to 840 ppm and Mo is up to 11.9 ppm) contents as well as high oxidation state (fO2 > fayalite-magnetite-quartz oxygen buffer) are featured in the quartz monzonite, indicating that the asthenospheric mantle source had been hydrated and oxidized by the water released from the stagnant Paleo-Pacific slab in the transition zone (410–610 km). Such modification by the deep stagnant oceanic slab beneath the eastern NCC thus not only triggered the remarkable thinning of the Archean lithospheric keel (loss of > 120 km), but also promoted the asthenospheric mantle to become the favorable magma and metal source for the Cu-Mo deposits in the study region.