We use historical and recent major earthquakes and GPS geodetic data to compute seismic strain rate, geodetic slip deficit, static stress drop, the parameters of the magnitude–frequency distribution and geodetic strain rate in the Iranian Plateau to identify seismically mature fault segments and regions. Our analysis suggests that 11 fault segments are in the mature stage of the earthquake cycle, with the possibility of generating major earthquakes. These faults primarily are located in the north and the east of Iran. Four seismically mature regions in southern Iran with the potential for damaging strong earthquakes are also identified. We also delineate four additional fault segments in Iran that can generate major earthquakes without robust clues to their maturity.The most important fault segment in this study is the strike-slip system near the capital city of Tehran, with the potential to cause more than one million fatalities.