One of the world's largest internally drained (endorheic) basins, the 1.14 million km2 Lake Eyre (hydrological) Basin (LEB), covers nearly 15% of the Australian continent. Palaeoclimatic and associated flow regime variations are recorded in an archive of fluvial, aeolian and lacustrine sediments that are particularly accessible for deposits from the past ~ 300 ka, and are especially relevant for the past ~ 50 ka during which humans have inhabited Australia. Due to its great size, economic resources and diverse latitudinal extent, it has for over six decades been the focus of environmental, scientific and resource-based studies across numerous disciplines. With an emphasis on assessing the scientific and environmental research over this period, this paper is divided into four parts: Part A provides an introduction and background. Part B provides the geological history, including evidence of substantial Tertiary and Quaternary climate change. Part C covers the contemporary environmental conditions, and Part D presents a conclusion and summary. This not only represents the first comprehensive review of current knowledge of any of the world's truly large dryland drainage basins, but also highlights how more multi-disciplinary research is required. Key remaining questions revolve around the impact of global weather systems on the LEB; the lake-level story in relation to a more precise picture of Late Quaternary climate change; the role of humans and climate in the demise of the megafauna; modern hydrological changes; the role of vegetation in altering channel morphology and flow efficiencies; and nature of flood transmissions.