Optically stimulated luminescence (OSL) ages from a relict shoreline on Lake Callabonna record a major pluvial episode in southern central Australia between 1050 ± 70 and 1100 ± 60 Common Era (CE), within the Medieval Climatic Anomaly (MCA). During this pluvial interval Lake Callabonna filled to 10–12 times the volume of the largest historical filling (1974) and reached maximum depths of 4–5 m, compared to the 0.5–1.0 m achieved today. Until now there has been no direct evidence for the MCA in the arid interior of Australia. A multi-proxy, analogue-based atmospheric circulation reconstruction indicates that the pluvial episode was associated with an anomalous meridional atmospheric circulation pattern over the Southern extratropics, with high sea-level pressure ridges in the central Indian Ocean and Tasman Sea, and a trough extending from the Southern Ocean into central Australia. A major decline in the mobility of the Australian aboriginal hunter-gatherer coincides with this MCA period, in southern central Australia.