The Early Paleozoic paleogeographic locations of the Tibetan terranes in Gondwana remain poorly constrained. This study reports petrology, zircon LA-ICP-MS U-Pb ages, whole-rock major and trace element compositions, and Sr-Nd-Hf isotopic data for the gneissic granites in the Amdo microcontinent, central Tibetan Plateau. LA-ICP-MS zircon U-Pb dating yielded Cambrian ages of ca. 500 Ma for the granites. A Cryogenian age of ca. 800 Ma was recognized from inherited zircons. Geochemical data indicate that these granites belong to high-K calc–alkaline I-type granitoids. They mostly exhibit negative values of zircon ε_Hf(t) (−7.1 to +0.1) and whole-rock ε_Nd(t) (−5.9), as well as old zircon Hf model ages (T^C_DM = 1718–1472 Ma) and whole-rock Nd model ages (T^C_DM = 1771 and 1777 Ma). These granites can be interpreted as resulting from partial melting of ancient crustal materials that have been modified by mantle-derived magmas. Integrating previous magmatic studies with the data presented in this contribution, we suggest that the Amdo microcontinent was linked to the Indian Gondwanan margin and recorded the arc-related magmatism along the proto-Tethyan margin.