The head of a mantle plume can weaken the oceanic lithosphere through the combined action of its buoyancy forces and excess temperature, which eventually induces intra-oceanic subductions. However, the dynamics of plume-induced subductions, their lifetime and their ability to propagate at the scale of an entire ocean remain unknown. Here, we combine a quantitative synthesis of the ophiolitic record of the Neotethys subduction in the Late Cretaceous with 3D spherical modeling of mantle convection self-generating plate-like tectonics to propose that the pre-Deccan plume initiated the Southern Neotethys Subduction. We suggest that this subduction retreated at 5-10 cm yr−1 until it reached the continental margins of Arabia and India. The sequential segmentation of this subduction during its retreat and the diachronous deactivation of the resulting segments drove the Late Cretaceous-Eocene series of plate reorganization events recorded in the Indian Ocean's fabric.