The long-term climate transition from the Cretaceous greenhouse to the late Paleogene icehouse provides an opportunity to study changes in Earth system dynamics associated with large changes in global temperature and atmospheric CO2 levels. Elevated CO2 levels during the mid-Cretaceous supergreenhouse interval (~95–80 Ma) resulted in low meridional temperature gradients, and oceanic deposition during this time was punctuated by widespread episodes of severe anoxia termed oceanic anoxic events, resulting in enhanced burial of organic carbon in conjunction with transient carbon isotope and temperature excursions. The prolonged interval of mid-Cretaceous warmth and subsequent Late Cretaceous–Paleogene climate trends, as well as intervening short-lived climate excursions, are poorly documented in the southern high latitudes. International Ocean Discovery Program (IODP) Expedition 392 aims to drill five sites in the southwest Indian Ocean on the Agulhas Plateau and in the Transkei Basin, positioned at paleolatitudes of 65°–58°S during the Late Cretaceous (100–66 Ma) and in the new and evolving gateway between the South Atlantic, Southern Ocean, and southern Indian Ocean basins. Recovery of basement rocks and expanded sedimentary sequences from the Agulhas Plateau and Transkei Basin will provide a wealth of new data to (i) determine the nature and origin of the Agulhas Plateau and (ii) significantly advance the understanding of how Cretaceous temperatures, ocean circulation, and sedimentation patterns evolved as CO2 levels rose and fell and the breakup of Gondwana progressed. Importantly, Expedition 392 drilling will test competing hypotheses concerning Agulhas Plateau large igneous province formation and the role of deep ocean circulation changes through southern gateways in controlling Late Cretaceous–Paleogene climate evolution.