The closure time of the Karamaili Ocean is the key to understand the accretionary history of the East Junggar at the southern Central Asian Orogenic Belt in the Paleozoic. In this study, we report geochronology, whole-rock elemental and Sr-Nd isotopic data and zircon Lu-Hf isotopic data of four Late Carboniferous to Early Permian I- and A-type granitic plutons in the Karamaili region in East Junggar, NW China. The Carboniferous Hongliuxia gneissic granite and the Hongliugou granodiorite yield zircon 206Pb/238U ages of 324 ± 1 Ma and 306 ± 1 Ma, respectively, and both of them are high-K calc-alkaline and belong to I-type granitoids. These granites show (87Sr/86Sr)i values from 0.7034 to 0.7046, ɛNd(t) values from 4.4 to 6.3, with Nd TDM2 model ages of 559–727 Ma; and ɛHf(t) values from 9.4 to 12.8, with Hf TDM2 model ages of 481–710 Ma. The variable positive Nd-Hf isotopic signature and young TDM2 model ages suggest that the I-type granitoids were derived from partial melting of juvenile crustal source, probably earlier arc intrusion. The Early Permian Daliugou and Mawangmiao plutons have 206Pb/238U ages of 297 ± 1 Ma and 284 ± 2 Ma, respectively, show high-K calc-alkaline to shoshonitic characteristics and belong to A2-type granite. They exhibit (87Sr/86Sr)i values from 0.7040 to 0.7065, ɛNd(t) values from 2.1 to 5.4, with Nd TDM2 model ages of 612–887 Ma; and ɛHf(t) values from 5.2 to 11.5, with Hf TDM2 model ages ranging from 548 Ma to 955 Ma, and the Nd-Hf isotope data also suggest that they were derived from juvenile crustal source. Mafic microgranular enclaves in the Daliugou pluton yield zircon 206Pb/238U age of 299 ± 2 Ma, and show similar geochemistry affinity with the granite host. The presence of enclaves and reverse zoning K-feldspars indicate that the magma mixing may have played an important role in the evolution of the Daliugou pluton. In this study, only the Hongliuxia gneissic granite was deformed, and a Nd-Hf isotopic transition occurred at ~300 Ma. Furthermore, the Late Carboniferous I-type granitoids from the Hongliuxia and the Hongliugou plutons show an arc affinity, and the Early Permian A-type granitoids from the Mawangmiao and the Daliugou plutons show post-collisional affinity. These lines of evidence enable us to argue that the Karamaili Ocean probably closed at a period between 324 Ma and 306 Ma. The post-collisional Early Permian magmatism in East Junggar was independent from the Tarim mantle plume.