The Hua’aobaote Pb-Zn-Ag Polymetallic orefield is situated in the southern section of the Great Xing’an Range (GXAR), which has experienced extensive magmatism. Since the Paleozoic, there are two stages of magmatism in Hua’aobaote orefield occurred in the Paleozoic and Mesozoic. The Mesozoic magmatism is of great significance for the Pb-Zn-Ag Polymetallic mineralization in Hua’aobaote orefield. In this study, new geochemical data was obtained to discuss the timing and petrogenesis of the magmatic rocks and its geodynamic and metallogenic significance. Zircon U-Pb ages reveal that the felsic igneous rocks from the Hua’aobaote orefield were formed in the Early Permian (294.8 ± 3.2 Ma) and Early Cretaceous (132.6 ± 1.4 Ma). Geochemically, the Early Permian granodiorite porphyrite is characterized by high Sr/Y (42–63) ratios and Mg# (62.24–70.74) values and low heavy rare earth element (HREE) (5.09–6.79 ppm) contents. The granodiorite porphyrite is also characterized by depleted Sr–Nd initial isotopic signatures [εNd(t) = 5.91–7.59, (87Sr/86Sr)i = 0.7029–0.7030], exhibiting adakitic characteristics. The Early Cretaceous granite porphyry and rhyolite are A-type felsic igneous rocks, and demonstrate high SiO2, Na2O + K2O and rare earth element (REE) contents, low CaO and MgO contents, low (87Sr/86Sr)i ratios (0.7044–0.7058), and positive εNd(t) values (2.57–4.65). Whole-rock Pb isotopic compositions in granodiorite porphyrite are: 206Pb/204Pb = 17.631–18.149, 207Pb/204Pb = 15.422–15.450, and 208Pb/204Pb = 37.325–37.729. The granite porphyry and rhyolite have initial 206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb ratios of 18.106–19.309, 15.489–15.539, and 37.821–38.05, respectively. Sr-Nd-Pb isotopic evidence suggests that the Early Permian granodiorite porphyrite is likely to derive from slab melts and modified by peridotitic mantle wedge in the subduction tectonic setting of the Paleo-Asian Ocean. The Early Cretaceous A-type felsic igneous rocks were derived from juvenile lower crust, accompanied by limited crustal contamination and various degree of fractional crystallisation during magma emplacement. The Early Cretaceous magmatism and related mineralization were formed in a post-orogenic tectonic setting that attributed to the closure of the Mongol–Okhotsk Ocean. Pb isotopic data for the various rock units in the study area indicate that the Mesozoic magma source contributed substantial Pb, Zn, and Ag to the Hua’aobaote deposit.