Contrasting geochemical signatures of copper ore hosting Eocene and some barren undeformed Miocene diorites to granites in central Iran temporally overlap with the Alpine-Himalayan collision and provide key implications on the existence and lack of Cu mineralization during collisional magmatism. High Sr and low Y (and Yb) contents of Eocene arc rocks in the Natanz arc segment reflect thickened, Andean-type orogenic arc crust (~45 km), whereas barren Miocene Natanz arc rocks (21–19 Ma) indicate thin arc crust similar to collisional volcanism in Anatolia. Geochemical modeling indicates a change in the mineralogy of the melt residual, from precollisional Eocene basaltic garnet-bearing (5–30%) amphibolite to syn- or postcollisional Miocene metasomatized mantle peridotite, which can be explained by collision-induced delamination of the arc lithospheric root. Subsequent recharge of hot asthenosphere and melting of metasomatized mantle peridotite and lack of interaction with a garnet-bearing arc crustal keel explain the low Sr and high Y (and Yb) contents, the relatively enriched initial Sr isotope ratios of postcollisional Miocene Natanz rocks, and the lack of copper mineralization in postcollisional Miocene Natanz arc rocks. Arc-root delamination removes the copper- and sulfur-enriched metasomatized lithospheric arc root and hydrous cumulate reservoir required to form copper ore deposits. Lack of the dense melt residues also provides an alternative explanation for the elevated, thin crustal Iranian back-arc plateau (38 km) as a result of uplift by isostatic rebound rather than uplift by anomalous shortening. Miocene arc-root delamination implies a minimum age of >21 Ma for the Alpine-Himalayan collision in central Iran.