The Neogene ignimbrite flare-up of the Altiplano Puna Volcanic Complex (APVC) of the Central Andes produced one of the best-preserved large silicic volcanic fields on Earth. At least 15 000 km3 of magma erupted as regional-scale ignimbrites between 10 and 1 Ma, from large complex calderas that are typical volcano-tectonic depressions (VTD). Simple Valles-type calderas are absent. Integration of field, geochronological, petrological, geochemical and geophysical data from the APVC within the geodynamic context of the Central Andes suggests a scenario where elevated mantle power input, subsequent crustal melting and assimilation, and development of a crustal-scale intrusive complex lead to the development of APVC. These processes lead to thermal softening of the sub-APVC crust and eventual mechanical failure of the roofs above batholith-scale magma chambers to trigger the massive eruptions. The APVC ignimbrite flare-up and the resulting VTDs are thus the result of the time-integrated impact of intrusion on the mechanical strength of the crust, and should be considered tectonomagmatic phenomena, rather than purely volcanic features. This model requires a change in paradigm about how the largest explosive eruptions may operate.