Plate tectonic history, geological, geochemical (element and isotope ratios), and seismological (P-wave tomography and SKS splitting) data are combined with laboratory modeling to present a three-dimensional reconstruction of the subduction history of the central Mediterranean subduction. We find that the dynamic evolution of the Calabrian slab is characterized by a strong episodicity revealed also by the discrete opening of the Tyrrhenian Sea. The Calabrian slab has been progressively disrupted by means of mechanical and thermal erosion leading to the formation of large windows, both in the southern Tyrrhenian Sea and in the southern Apennines. Windows at lateral slab edges have caused a dramatic reorganization of mantle convection, permitting inflow of subslab mantle material and causing a complicated pattern of magmatism in the Tyrrhenian region, with coexisting K- and Na-alkaline igneous rocks. Rapid, intermittent avalanches of large amounts of lithospheric material at slab edges progressively reduced the lateral length of the Calabrian slab to a narrow (200 km) slab plunging down into the mantle and enhancing the end of the subduction process.