The separation between Australia and Antarctica occurred during the final stages of the break-up of Pangea. Reconstructions of the rifting of the Australian plate away from Antarctica show fast spreading rates since Mid-Eocene (45 Ma). These reconstructions can be used to understand and quantify the forces driving the Australia/Antarctica separation, and to test hypotheses on mechanisms that may be of shallow (i.e., lithosphere) or deep (i.e., mantle) origin. Analytical calculations indicate that plate-boundary forces are highly unlikely to be a plausible candidate to explain such a separation. Thus, we use a recently developed global coupled models of mantle and lithosphere dynamics, here we show that this event, whose kinematics are reproduced in our models within the bounds of the reconstruction uncertainties, owes to a significant degree to the pressure-driven asthenospheric Poiseuille flow associated with the mantle buoyancy field inherited from viscous circulation history throughout the Mesozoic. On the contrary, in simulations when such a buoyancy field is replaced by another one resulting from a random distribution of mantle temperature-thus not representative of Earth's mantle circulation history-the rapid northward motion of Australia does not occur. Similarly, suppressing contemporaneous plate-boundary processes (i.e., subduction of the Pacific ridge at the Aleutians and healing of the India-Australia ridge) from our models does not have a noticeable effect on the Australia-Antarctica kinematics. Thus, a pressure-driven Poiseuille mantle flow must be considered, at least in this example and possible elsewhere, as a main driver of plate tectonics.