Luminescence dating at the stratified prehistoric site of Attirampakkam, India, has shown that processes signifying the end of the Acheulian culture and the emergence of a Middle Palaeolithic culture occurred at 385 ± 64 thousand years ago (ka), much earlier than conventionally presumed for South Asia. The Middle Palaeolithic continued at Attirampakkam until 172 ± 41 ka. Chronologies of Middle Palaeolithic technologies in regions distant from Africa and Europe are crucial for testing theories about the origins and early evolution of these cultures, and for understanding their association with modern humans or archaic hominins, their links with preceding Acheulian cultures and the spread of Levallois lithic technologies. The geographic location of India and its rich Middle Palaeolithic record are ideally suited to addressing these issues, but progress has been limited by the paucity of excavated sites and hominin fossils as well as by geochronological constraints. At Attirampakkam, the gradual disuse of bifaces, the predominance of small tools, the appearance of distinctive and diverse Levallois flake and point strategies, and the blade component all highlight a notable shift away from the preceding Acheulian large-flake technologies. These findings document a process of substantial behavioural change that occurred in India at 385 ± 64 ka and establish its contemporaneity with similar processes recorded in Africa and Europe. This suggests complex interactions between local developments and ongoing global transformations. Together, these observations call for a re-evaluation of models that restrict the origins of Indian Middle Palaeolithic culture to the incidence of modern human dispersals after approximately 125 ka.