The Eastern Tianshan provides significant insights in relation to unraveling the history of Early Paleozoic magmatism, ocean-continent transition, and tectonic evolution of the southern Central Asian Orogenic Belt. This investigation represents a detailed geochronological and geochemical study of the Early Paleozoic volcanic rocks from the Harlik and Dananhu terranes in the Eastern Tianshan. UPb zircon ages indicate periods of volcanism in Harlik Early Silurian (441–434 Ma) and Dananhu Late Ordovician (448–445 Ma). The Harlik Early Silurian volcanic rocks unconformably overlie Ordovician sediments, and consist of alkaline (434 Ma) and tholeiitic (440 Ma) basalts. The alkaline basalts originated from low degree partial melting of previously subduction-modified lithosphere and subsequent interaction with upwelling asthenosphere. The tholeiitic basaltic magmas were derived from partial melting of a spinel facies lithospheric mantle source metasomatized by early slab-derived fluids, which then underwent crystal fractionation of clinopyroxene and olivine. In contrast, the Dananhu Late Ordovician high-Mg andesites were generated by partial melting of a hydrous, depleted mantle wedge and these melts experienced a low degree of crystal fractionation. Combined with results from previous geological studies, it is proposed that the Harlik and Dananhu terranes had different volcanism and tectonic histories. The Harlik tholeiitic basalts were generated in a post-collision setting, which may be associated with the closure of the Armantai Ocean. Contrarily, the alkaline basalts were formed in an intraplate setting during the initial stages of intracontinental extension that gave rise to the Karamaili Ocean. The Dananhu Late Ordovician andesites represent the initial phase of arc-related volcanism due to the subduction of the North Tianshan Ocean, where the Dananhu arc may have temporally evolved from an Andean- to oceanic island-type arc in Early Paleozoic.