The Murray Basin is a low-lying but extensive intracratonic depocentre in southeastern Australia, preserving an extraordinary record of Late Neogene sedimentation. New stratigraphic and sedimentologic data allow the long-term evolution of the basin to be re-evaluated and suggest a significant role for: (1) tectonism in controlling basin evolution, and (2) progressive and step-wise climatic change beginning in the early Pleistocene. Tectonic change is associated with regional uplift, occurring at approximately the same rate from the early Pliocene until the present day, and possibly associated with changing mantle circulation patterns or plate boundary processes. This uplift led to the defeat and re-routing of the Murray River, Australia’s major continental drainage system. Key to our interpretation is recognition of timing relationships between four prominent palaeogeographic features – the Loxton-Parilla Sands strandplain, the Gambier coastal plain, palaeo megalake Bungunnia and the Kanawinka Escarpment. Geomorphic and stratigraphic evidence suggest that during the Early Pliocene the ancestral Murray River was located in western Victoria, flowing south along the Douglas Depression. Relatively small amounts of regional uplift (