Remnants of the Proto-Tethys are mainly preserved in the region between south of the North China-Tarim Block and north of Qiangtang-Sibumasu/Baoshan Blocks. Magmatic-metallogenic events related to the Proto-Tethyan subductions were rarely reported, and the subduction history and polarity of the Proto-Tethyan are still under debate. Here, we presented new data of zircon UPb ages, whole-rock Sr–Nd–Pb isotopes, major and trace elements and zircon Hf isotopes for the volcanic rocks in the northeastern Altyn Mountains. Information of over 14 volcanic-hosted deposits/prospects in the region has been compiled. These volcanic ore hosts consist mainly of basaltic andesite, andesite, dacite and rhyolite rocks. The andesite and rhyolite rocks are newly zircon UPb dated to be Late Cambrian-Early Ordovician (andesite: 490.5 ± 5.2 Ma; rhyolite: 492.6 ± 2.9 Ma and 491.6 ± 5.6 Ma), representing the timing of volcanism and VMS (Volcanogenic Massive Sulfide) mineralization. All the volcanic rocks belong to the high-K calc-alkaline and shoshonite series: the andesite rocks from the Kaladawan area in north of the region display arc geochemical affinities and contain (⁸⁷Sr/⁸⁶Sr)_i (0.7082–0.7083) and ε_Nd(t) (−9.7 to −7.6), indicating that they were likely formed by partial melting of the mantle wedge with subducted sediment inputs. The rhyolite rocks from the Kaladaban area in south of the region are characterized by high SiO₂ (64.46–78.55 wt%), low alkali (Na₂O + K₂O, 3.46–7.17 wt%), and contain (⁸⁷Sr/⁸⁶Sr)_i (0.7063–0.7095), ε_Nd(t) (−6.6 to −1.5), and zircon ε_Hf(t) (−5.5 to 5.4), indicating that they were likely derived from partial melting of the lower crust with depleted mantle inputs. Rock assemblage and geochemistry suggest that volcanic rocks in the northeastern Altyn Mountains may have formed in a continental arc setting. Their spatial distributions with respect to the ophiolites in the region suggest that the subduction was likely south-dipping. This subduction-related arc magmatism may have formed the many important VMS and porphyry–skarn deposits in the region.