The Penacova-Régua-Verin (PRV) and the Manteigas-Vilariça-Bragança (MVB) are two of the longest faults of the Iberian Peninsula. These faults striking NNE–SSW, over lengths of >200 km, were developed during late-Variscan Orogeny and reactivated in response to the Alpine Cycle tectonics. Their tectonic evolution during Alpine compression (Cenozoic) and their implication in the active tectonic activity of Iberia are under discussion. Their recent tectonic activity is recorded in the vertical offset of geomorphological surfaces, in the associated pull-apart basins, and in M > 7 paleoseismic events. Based on the vertical surface offset of Pliocene surfaces (140–300 m for the MVB fault and 150–200 m for the PRV), together with the horizontal offset (1300–1600 m for MVBF fault and 600–1400 m for PRVF), we can conclude that they were reactivated as left-lateral strike-slip faults with a reverse component during the Pliocene (3.6 Ma)–present. These results indicate that these faults are not related to the strain transmission during the collision with Eurasia (Eocene–Oligocene). However, they are related to the intraplate strain of the southern collision with the African plate during the Upper Neogene. The estimated slip-rate is 0.2–0.5 mm/a for both faults. These slip-rates evidence important implications for the seismic hazard of this intraplate region.