The Ullum-Zonda tectonic depression located in the central Andes Precordillera records several lacustrine episodes from frequent natural damming of the San Juan River during the late Quaternary. We analyzed stratigraphic, geomorphic, and geologic data and obtained new radiocarbon ages for Paleolake Ullum-Zonda. Results show the existence of a late Pleistocene age (16.7–15.2 ka BP) unit and an early to middle Holocene (9475–7685 yr BP) unit. Subsurface data show lacustrine episodes were common during the late Pleistocene, with probably nine episodes occurring during that period. Two transgressive events are evident in the Holocene unit, dated to ~8420±30 and shortly after 7460±30 14C yr BP. The maximum extent of the paleolake occurred at 6930±30 14C yr BP, shortly before the lake desiccated. Fault propagation folds and growth strata in Quaternary alluvial deposits relate to the Villicum-Zonda Fault and may indicate early to middle Holocene activity for this fault. The deformation observed in an ancient shoreline of the paleolake could be related to middle to late Holocene activity of the Cerro Zonda Norte Fault at a mean vertical uplift rate of ~0.8 mm/yr in the hanging wall block.