We report the first study integrating in situ U–Pb and Hf isotope data from magmatic zircon and whole-rock Sm–Nd isotope data for granitic rocks of the Sierras Pampeanas, Argentina, in order to evaluate the Palaeozoic growth of the proto-Andean margin of Gondwana. Early–Middle Ordovician granitic magmatism is by far the most voluminous of the Sierras Pampeanas and represents the most significant magmatic event. These calc-alkaline granitoids were intruded at an active continental margin. ε_Hft values range from −3.3 to −14.7 and ε_Ndt from −3.3 to −6.3 (t=473Ma), with average T_DM Hf and T_DM Nd ranging from 1.5 to 2.2Ga and 1.4 to 1.7Ga, respectively. Middle–Late Devonian magmatism occurred in the foreland, away from the orogenic front in the west, and included F-U-REE rich A-type granites. The Achala granite, the largest batholith in the Sierras Pampeanas, has ε_Hft and ε_Ndt values ranging from −3.6 to −5.8 and −4.0 to −6.5, respectively (t=369Ma). Small scattered Early Carboniferous A-type granite plutons were intruded in a dominantly extensional setting and have ε_Hft and ε_Ndt values ranging from −6.7 to +2.2 and −0.5 to −3.6, respectively (t=341Ma). The generation of Ordovician and Devonian magmas dominantly involved crustal reworking and stabilization rather than the formation of new continental crust by juvenile material accretion, whereas Carboniferous magmatism resulted in part from reworking of supracrustal material, but with variable addition of juvenile magmas.