The genesis and evolution of migmatite-granite terranes usually involve several complex petrological and geochemical processes that leave their imprint on elemental and isotopic signatures. In this paper, we assess the role of melting reactions on the genesis of the variscan Figueira de Castelo Rodrigo-Lumbrales Anatectic Complex (FCR-LAC) in the Central Iberian Zone that culminated in the generation of abundant S-type granites. At odds with the proposed for several anatectic complexes elsewhere, here we demonstrate that no isotopic (Sr-Nd-Hf-Pb) disequilibrium occurred in the FCR-LAC, either in the transitions from metatexites to diatexites nor to granites. However, variable contribution of the source minerals generated batches of melts characterized by distinct parent/daughter ratios, which explain the significant heterogeneity of present-day isotopic signatures. While Rb/Sr ratios and the Pb budget of the successively generated lithotypes were mainly controlled by major minerals such as muscovite, K-feldspar and plagioclase, the accessory phases played a major control on the Sm/Nd and Lu/Hf ratios. Our study also demonstrates the existence of two distinct diatexite groups produced by different melting reactions. Type-1 diatexites, having high Rb contents and fractionated HREE, are geochemically akin to the associated S-type granites. They were produced by dehydration-melting of muscovite with production of peritectic K-feldspar, sillimanite and melt. The less abundant type-2 diatexites required influx of external fluids for melting, which consumed more plagioclase than muscovite. Isotopic data reveal the existence of two groups with distinct initial compositions (εNd320 = −5.05 to −6.03 and εHf320 = −3.42 to −4.45 vs. εNd320 = −7.30 to −8.89 and εHf320 = −6.45 to −8.47), both composed of metatexites, diatexites and granites, due to source heterogeneity. The main source of the anatectic complex was the metasedimentary Neoproterozoic – lower Cambrian Douro-Beiras Supergroup, with minor contribution of Ordovician, Ollo de Sapo magmatic rocks.