New high-resolution MC-ICPMS U/Th ages and C and O isotopic analyses from a Holocene speleothem in arid south-central Australia provide evidence for increased effective precipitation (EP) relative to present at c. 11.5 ka and c. 8-5 ka, peak moisture at 7-6 ka, and onset of an arid climate similar to present by c. 5 ka. δ 18 O and δ 13 C time-series data exhibit marked (>+1‰) contemporaneous excursions over base-line values of −5.3‰ and −11.0‰, respectively, suggesting pronounced moisture variability during the early middle Holocene 'climatic optimum'. Optically stimulated luminescence and 14 C ages from nearby terraced aggradational alluvial deposits indicate a paucity of large floods in the Late Pleistocene and at least five large flood events in the last c. 6 kyr, interpreted to mark an increased frequency of extreme rainfall events in the middle Holocene despite overall reduced EP. Increased EP in south-central Australia during the early to middle Holocene resulted from (1) decreased El Niño-Southern Oscillation (ENSO) variability, which reduced the frequency of El Niño-triggered droughts, (2) the prevalence of a more La Niña-like mean climatic state in the tropical Pacific Ocean, which increased available atmospheric moisture, and (3) a southward shift in the Intertropical Convergence Zone (ICTZ), which allowed tropical summer storms associated with the Australian summer monsoon (ASM) to penetrate deeper into the southern part of the continent. The onset of heightened aridity and apparent increase in large flood frequency at c. 5 ka is interpreted to indicate the establishment of an ENSO-like climate in arid Australia in the late Holocene, consistent with a variety of other terrestrial and marine proxies. The broad synchroneity of Holocene climate change across much of the Australian continent with changes in ENSO behavior suggests strong teleconnections amongst ENSO and the other climate systems such as the ASM, Indian Ocean Dipole, and Southern Annular Mode.