This study is an attempt to unravel the tectono-metamorphic history of high-grade metamorphic rocks in the Eastern Erzgebirge region. Metamorphism has strongly disturbed the primary petrological genetic characteristics of the rocks. We compare geological, geochemical, and petrological data, and zircon populations as well as isotope and geochronological data for the major gneiss units of the Eastern Erzgebirge; (1) coarse- to medium-grained “Inner Grey Gneiss”, (2) fine-grained “Outer Grey Gneiss”, and (3) “Red Gneiss”. The Inner and Outer Grey Gneiss units (MP-MT overprinted) have very similar geochemical and mineralogical compositions, but they contain different zircon populations. The Inner Grey Gneiss is found to be of primary igneous origin as documented by the presence of long-prismatic, oscillatory zoned zircons (540 Ma) and relics of granitic textures. Geochemical and isotope data classify the igneous precursor as a S-type granite. In contrast, Outer Grey Gneiss samples are free of long-prismatic zircons and contain zircons with signs of mechanical rounding through sedimentary transport. Geochemical data indicate greywackes as main previous precursor. The most euhedral zircons are zoned and document Neoproterozoic (ca. 575 Ma) source rocks eroded to form these greywackes. U-Pb-SHRIMP measurements revealed three further ancient sources, which zircons survived in both the Inner and Outer Grey Gneiss: Neoproterozoic (600-700 Ma), Paleoproterozoic (2100-2200 Ma), and Archaean (2700-2800 Ma). These results point to absence of Grenvillian type sources and derivation of the crust from the West African Craton. The granite magma of the Inner Grey Gneiss was probably derived through in situ melting of the Outer Grey Gneiss sedimentary protolith as indicated by geological relationships, similar geochemical composition, similar Nd model ages, and inherited zircon ages. Red Gneiss occurs as separate bodies within fine- and medium-grained grey gneisses of the gneiss-eclogite zone (HP-HT overprinted). In comparison to Grey Gneisses, the Red Gneiss clearly differs in geochemical composition by lower contents of refractory elements. Rocks contain long-prismatic zircons (480-500 Ma) with oscillatory zonation indicating an igneous precursor for Red Gneiss protoliths. Geochemical data display obvious characteristics of S-type granites derived through partial melting from deeper crustal source rocks. The obtained time marks of magmatic activity (ca. 575 Ma, ca. 540 Ma, ca. 500-480 Ma) of the Eastern Erzgebirge are compared with adjacent units of the Saxothuringian zone. In all these units, similar time marks and geochemical pattern of igneous rocks prove a similar tectono-metamorphic evolution during Neoproterozoic-Ordovician time.