The distinct submarine volcanic-hosted iron ore deposits in the Awulale Iron Metallogenic Belt are the most important sources for iron in the Chinese Western Tianshan metallogenetic province, although, the exact tectonic setting for their formation remains poorly constrained. A compilation of published and new geochronological and geochemical data suggests a protracted magmatism from ca. 450 to 290 Ma was in close spatial and temporal proximity to the iron deposits. The different magmatic rocks have broadly similar arc-like geochemical signatures such as LREE and LILE enrichments, HREE and HFSE depletions, Nb–Ta–Ti negative anomalies and flat HREE patterns, all of which are attributed to magmatic differentiation and/or partial melting in relatively thin crust due to long-term extension. The contrasting whole-rock Nd isotopic patterns of the igneous rocks and the well-defined peak metamorphism (ca. 320–310 Ma) of the subduction-zone high-pressure rocks indicate that ca. 450–321 Ma magmatic rocks with an increasingly positive εNd(t) shift were formed during the northward subduction of the South Tianshan Ocean, where slab rollback resulted in an extensional setting in the southern Yili-Central Tianshan Block. In contrast, the synchronicity of the ca. 320–310 Ma subduction-zone peak metamorphism and magmatic flare-up with uniformly positive εNd(t) values is interpreted as the consequence of slab break-off subsequent to the oceanic subduction and the continental collision. By inference, the late-stage (ca. 309–290 Ma) magmatism was likely constructed in a post-collisional setting. The submarine volcanic-hosted iron mineralization exclusively occurred coeval with the peak metamorphism and intensive magmatism, probably suggesting slab break-off as the exact tectonic setting for iron mineralization. Consequently, the western extension of the Awulale Iron Metallogenic Belt occurring roughly parallel to the South Tianshan Orogen may have significant potential for prospecting the submarine volcanic-hosted iron ore deposits.