The Famatinian orogeny along the proto-Pacific margin of Gondwana, from Venezuela to northeastern Patagonia, was of the accretional type during the Paleozoic (Ordovician to Silurian). Information gathered from the Sierras Pampeanas (Argentina) reveals magmatism (plutonism and volcanism) between 490 and 465 Ma, with a peak at 473–467 Ma, similar to other regions along the margin. Metamorphic events in the middle crust occurred between 484 and 465 Ma, and at ca. 440 Ma. Recent reviews propose a lithospheric extension phase (>480 Ma) before contraction episodes (ca. 470 and 440 Ma). Magmatism transitioned from peraluminous to metaluminous intrusions, with prolonged mafic magmatism throughout. Mafic intrusions show a broad spectrum of isotope compositions (87Sr/86Srt = 0.705 to 0.711 and ƐNdt = +5 to −6) but with general trends toward isotopically enriched magmas. The main arc consists of tonalite-granodiorite magmas (ca. 480–470 Ma) with <25% crustal contamination but crustal-like isotopic signatures (87Sr/86Srt = 0.707 to 0.711 and ƐNdt = −4 to −6). The wide isotopic variations in granodiorite-monzogranite (and volcanic equivalents) (87Sr/86Srt = 0.705 to 0.711 and ƐNdt = +3 to −6) suggest two origins: differentiation and contamination of tonalite-granodiorite magmas (AFC model) for the most evolved, and differentiation from juvenile mafic additions for the isotopically juvenile ones. Regardless of depth (∼1–6 kbar) and position within the magmatic arc, analyzed areas display north-south striking and steep magmatic fabrics. These fabrics may have rotated by no more than 20–28° from its original position. The petrogenetic model involves isotopically diverse sub-arc mantle sources. Famatinian magmatism ceased abruptly around 465 Ma (magmatic lull), correlating with arcs along the SW Gondwana margin, indicating significant geodynamic changes in the subduction regime.