The Chinese East Tianshan is the easternmost sector of the Tianshan Mountain Range in the Central Asian Orogenic Belt (CAOB), and accommodates several events of magmatism, crustal growth and mineralization. The Kalatag arc is unique in the East Tianshan due to its widespread Early Paleozoic volcanic rocks, which offers a special opportunity to study the Early Paleozoic Cu-dominant mineral systems in island arc setting. In this region nine deposits have been discovered in recent years. These deposits occur in Paleozoic volcanic rocks between the Kalatag Fault and Kabei Fault, and can be divided into six mineral systems, i.e., VMS Cu-Zn, epithermal Cu, porphyry Cu-Au, skarn Fe-Cu, magmatic Cu-Ni sulfide and hydrothermally overprinted deposits. Among them, VMS, epithermal, porphyry-skarn and magmatic Cu–Ni sulfide mineralization are distributed in the southeastern, central, northwestern and westernmost Kalatag, respectively. The mineralization and associated intrusive rock ages can be clustered into four episodes in the Kalatag arc, i.e., Late Ordovician–Silurian (ca. 450–430 Ma), Middle Devonian (ca. 390–380 Ma), Late Carboniferous (ca. 320–300 Ma) and Permian (ca. 280 Ma). Here, Paleozoic granitoids show similar geochemistry and isotopic features. All Paleozoic granitoids plot in the subalkaline field, and predominantly tholeiitic to calc-alkaline series, with enrichment of large-ion lithophile elements and depletion of high-field-strength elements. These granitoids plot in a volcanic arc fields in tectonic discrimination diagrams, which are characteristic of an island arc setting. The fluid inclusions in porphyry and skarn system are characterized by high-temperature, high-salinity, low-content of CO2, whereas epithermal system represented by low-temperature, low-salinity, low-content of CO2, and the VMS system can be described as medium-temperature, medium low-salinity, CO2-bearing fluid. H-O isotopic data suggest that ore-fluids were sourced from a mixing fluid between magmatic and meteoric water. S-Pb isotopic data show that the sulfur mainly came from magma or ore-hosting igneous rocks. The Yudai porphyry Cu-Au deposit, the Hongshi epithermal Cu deposit and the Honghai Au-rich VMS Cu-Zn deposit formed at the same time related to a subduction environment. The Early Paleozoic VMS mineralization is generally overprinted by late magmatic hydrothermal fluids, which may be due to multiple accretionary orogeny in Kalatag island arc. We propose that the north-dipping subduction of the Paleo-Tianshan Ocean or south-dipping subduction of the Junggar Ocean during Late Ordovician–Silurian, which may led to the development of Yudai porphyry copper, Hongshi epithermal copper and Honghai VMS copper-zinc deposits in the Kalatag arc. After that, north-dipping subduction of the Paleo-Tianshan Ocean resulted to the formation of the Middle Devonian (ca. 390–380 Ma) and Late Carboniferous (ca. 320–300 Ma) Cu mineralization. Finally, the Permian (ca. 280 Ma) magmatic copper–nickel sulfide deposits associated with ultramafic–mafic complexes developed in post-collisional-extension setting, part of a Large Igneous Province (LIP) event associated with mantle plume upwelling.