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Caves often hold valuable palaeoclimate archives including speleothems, fossil remains, and clastic sediments that complement each other. This paper presents a multi-archive interdisciplinary study of an extensive deposit of fossil mammals from the scientific reserve in the Muierilor Cave, Southern Carpathians, Romania. We present two new palaeontological excavations that indicate a high abundance and diversity of MIS 3–2 fossil mammals (carnivores, omnivores and herbivores) synchronous with the early modern humans known from this cave. Using geochronological and sedimentological methods, we present a general reconstruction of the cave evolution between ~120 kyr B.P. and the Holocene. The study is based on a combination of geochronological tools including OSL dating of sediments, U/Th dating of speleothems, and radiocarbon dating of fossil remains, with a total of 54 ages. Based on U/Th dating of speleothems from stratigraphically-relevant positions, we show that the MIS 3 assemblage of fossil mammals were massively reworked and deposited during the post-LGM deglaciation, slightly earlier than previously known for the Southern Carpathians. On the other hand, several young radiocarbon ages of cave bear samples suggest that the Southern Carpathians might have been functioning as a glacial refuge for this species as late as ~22 kyr B.P.