Earth's mightiest ocean current, the Antarctic Circumpolar Current (ACC), regulates the exchange of heat and carbon between the ocean and the atmosphere, and influences vertical ocean structure, deep-water production and the global distribution of nutrients and chemical tracers. The eastward-flowing ACC occupies a unique circumglobal pathway in the Southern Ocean that was enabled by the tectonic opening of key oceanic gateways during the break-up of Gondwana (for example, by the opening of the Tasmanian Gateway, which connects the Indian and Pacific oceans). Although the ACC is a key component of Earth's present and past climate system, the timing of the appearance of diagnostic features of the ACC (for example, low zonal gradients in water-mass tracer fields) is poorly known and represents a fundamental gap in our understanding of Earth history. Here we show, using geophysically determined positions of continent-ocean boundaries, that the deep Tasmanian Gateway opened 33.5 ± 1.5 million years ago (the errors indicate uncertainty in the boundary positions). Following this opening, sediments from Indian and Pacific cores recorded Pacific-type neodymium isotope ratios, revealing deep westward flow equivalent to the present-day Antarctic Slope Current. We observe onset of the ACC at around 30 million years ago, when Southern Ocean neodymium isotopes record a permanent shift to modern Indian-Atlantic ratios. Our reconstructions of ocean circulation show that massive reorganization and homogenization of Southern Ocean water masses coincided with migration of the northern margin of the Tasmanian Gateway into the mid-latitude westerly wind band, which we reconstruct at 64° S, near to the northern margin. Onset of the ACC about 30 million years ago coincided with major changes in global ocean circulation and probably contributed to the lower atmospheric carbon dioxide levels that appear after this time.