In order to investigate their precise geochronological framework, petrogenesis, and tectonic implications, whole-rock major and trace elements, together with zircon U–Pb and Hf isotope data, are reported for the Mo-bearing granitoids from the eastern Jilin-Heilongjiang provinces in the eastern segment of the Central Asian Orogenic Belt. Zircon U–Pb dating by LA–ICP–MS yields crystallization ages for the Liushengdian monzogranite porphyry (252.2 ± 1.6 Ma), the Luming monzogranite porphyry (197.1 ± 1.6 Ma), and the Baoshan granodiorite (164.4 ± 1.9 Ma) and quartz diorite (165.2 ± 1.7 Ma), respectively. This zircon U–Pb data, combined with previous ages, indicate that the eastern Jilin-Heilongjiang provinces is dominated by 2 stages of ore-related granitic magmatism and associated Mo mineralization, that is, Late Permian (259–252 Ma) and Early-Middle Jurassic (200–165 Ma). Geochemically, these Mo-bearing granitoids have high SiO2 (60.78–74.67 wt.%) and K2O (2.85–6.23 wt.%), low MgO (0.17–2.85 wt.%) and CaO (0.66–4.38 wt.%) contents, with A/NCK and δEu values of 0.87–1.08 and 0.19–1.07, respectively; we infer that they belong to high-K calc-alkaline series and are metaluminous to peraluminous in nature. They are characterized by enrichment in large ion lithophile elements and light rare earth elements, and weak depletion in high field strength elements and heavy rare earth elements, consistent with the geochemical signatures of subduction-related genesis. In addition, in situ Hf isotopic analyses of zircons from 4 dated samples reveal that they have εHf(t) values of −0.4 to +10.3, with 2-stage model ages varying from 551 to 1,261 Ma, indicating that they probably originated from the partial melting of a dominantly Mesoproterozoic–Neoproterozoic crustal source. On the basis of the geochemical data and regional geological investigations, we propose that the formation of the Late Permian Mo-bearing granite was related to the subduction of the Paleo-Asian Ocean plate, whereas the generation of the Early-Middle Jurassic Mo-bearing granitoids was associated with the subduction of the Paleo-Pacific Plate beneath the Eurasian continent.