The Sierra de Pie de Palo, in the Argentinean Sierras Pampeanas (Andean foreland), consists of a Mesoproterozoic basement and an Ediacaran – upper Cambrian sedimentary cover that underwent folding, thrusting and metamorphism during the Ordovician Famatinian orogeny. Mafic rocks and granitoids of the easternmost Sierra de Pie de Palo provide information about the magmatic activity at the proto-Andean margin of Gondwana during late Cambrian – Early Ordovician time. Magmatic activity began in the Sierra de Pie de Palo as dykes, sills and small intrusions of tholeiitic gabbros between 490 and 470 Ma, before shortening and regional metamorphism. Variable mantle sources (Nd depleted mantle age, TDM between 1.7 and 1.3 Ga) were involved in the mafic magmatism. Nd-isotope signatures were probably inherited from a Mesoproterozoic subcontinental mantle. Mafic magmatism was coincident with collapse of a Cambrian carbonate-siliciclastic platform that extended along SW Gondwana, and was probably coeval with the beginning of subduction. After mafic magmatism, peraluminous granitoids were emplaced in the Sierra de Pie de Palo along ductile shear zones during a contractional tectonic phase, coeval with moderate to high P/T metamorphism, and with the Cordilleran-type magmatic arc that resulted from a flare-up at c. 470 Ma. Granitoids resulted mainly from partial melting of metasedimentary rocks, although some hybridization with juvenile magmas and/or rocks cannot be ruled out. The evidence shown here further implies that the Pie de Palo block was part of the continental upper plate during the Famatinian subduction, and not an exotic block that collided with the Gondwana margin.