We present U–Pb zircon crystallization ages combined with major and trace element analyses, Sr–Nd isotopes and zircon in-situ Hf isotope analyses of intermediate to granitic intrusions along the southern segment of the N-S trending Sistan suture zone in eastern Iran. The Zahedan and Shah-Kuh Eocene plutons consist in a series of granite–granodiorite–rhyolite with U–Pb zircon ages of 40.5–44.3 Ma and ca. 28.9–30.9 Ma. Isotope geochemistry and modeling suggest that 40.5–44.3 Ma plutons represent melts derived from the turbidites of the surrounding accretionary wedge. Melting of the wedge was induced by the intrusion of mantle magmas, with subsequent interaction between mantle- and turbiditic melts being responsible for the wide range of compositions. Most of the 28.9–30.9 Ma magmas were generated from mantle melting, with assimilation of the surrounding turbidites. The rare setting of within-wedge intrusions is attributed to mantle upwelling reaching wedge sediments at the inception of delamination processes, which signal the end of subduction-related deformational and thermal events in the Sistan suture zone.