From a detailed study of a 500 km transect in the Sierras Pampeanas, central-west Argentina, two pre-Silurian tectono-magmatic episodes are recognized and defined, each culminating in micro-continental collisions against the proto-Andean margin of Gondwana. The Pampean orogeny started in Early Cambrian time with short-lived subduction, indicated by ca. 535 Ma calc-alkaline granitoids. Following Pampean terrane collision, burial to granulite facies conditions (ca. 9 kbar) generated widespread migmatites and ca. 520 Ma highly peraluminous granites in the Eastern Sierras Pampeanas. After brief quiescence, a second major episode, the Famatinian orogeny, started with subduction ca. 490 Ma, forming a wide continental arc and ensialic backarc basin. This heralded the approach of Laurentia to Gondwana, during which the Precordillera terrane separated from the southern Appalachian region, finally colliding with Gondwana in Silurian–Devonian time.