Evaluating the role of tectonics and climate as possible triggering mechanisms of landscape reconfigurations is essential for paleoenvironmental and paleoclimatic reconstructions. In this study an exceptional receptive closed Quaternary system of Patagonia (the Gastre Basin) is described, and examined in order to analyze factors triggering base-level drops. Based on a geomorphological approach, which includes new tectonic geomorphology investigations combined with sedimentological and stratigraphic analysis, three large-scale geomorphological systems were identified, described and linked to two major lake-level highstands preserved in the basin. The results indicate magnitudes of base-level drops that are several orders of magnitude greater than present-day water-level fluctuations, suggesting a triggering mechanism not observed in recent times. Direct observations indicating the occurrence of Quaternary faults were not recorded in the region. In addition, morphometric analyses that included mountain front sinuosity, valley width-height ratio, and fan apex position dismiss tectonic fault activity in the Gastre Basin during the middle Pleistocene–Holocene. Therefore, we suggest here that upper Pleistocene climate changes may have been the main triggering mechanism of base-level falls in the Gastre Basin as it is observed in other closed basins of central Patagonia (i.e., Carri Laufquen Basin).