The Moringa Cave within Pleistocene sediments in the En Gedi area of the Dead Sea Fault Escarpment contains a sequence of various Pleistocene lacustrine deposits associated with higher-than-today lake levels at the Dead Sea basin. In addition it contains Chalcolithic remains and 5th century BC burials attributed to the Persian period, cemented and covered by Late Holocene travertine flowstone. These deposits represent a chain of Late Pleistocene and Holocene interconnected environmental and human events, echoing broader scale regional and global climate events. A major shift between depositional environments is associated with the rapid fall of Lake Lisan level during the latest Pleistocene. This exposed the sediments, providing for cave formation processes sometime between the latest Pleistocene (ca. 15 ka) and the Middle Holocene (ca. 4500 BC), eventually leading to human use of the cave. The Chalcolithic use of the cave can be related to a relatively moist desert environment, probably related to a shift in the location of the northern boundary of the Saharo-Arabian desert belt. The travertine layer was U–Th dated 2.46"0.10 to 2.10"0.04 ka, in agreement with the archaeological finds from the Persian period. Together with the inner consistency of the dating results, this strongly supports the reliability of the radiometric ages. The 2.46–2.10 ka travertine deposition within the presently dry cave suggests a higher recharge of the Judean Desert aquifer, correlative to a rising Dead Sea towards the end of the 1st millennium BC. This suggests a relatively moist local and regional climate facilitating human habitation of the desert.