Laguna de las Nutrias is a small/enclosed shallow lake located within an environmentally protected area under negligible anthropogenic impact in Southeastern South America (SESA). It holds a high-resolution sedimentary record that allowed us to infer the hydrological response to the regional climatic variability during the last 700 year linked to different climate variability modes. We performed 2 mm-µXRF-scanning analyses on an 88-cm long sediment core, which was dated by both 14C and 210Pb techniques. We utilized Ti/Al, Ti/Ca, Fe/Mn, Ti/K, S/Ti, Br/Ti, and Si/Ti as proxies for catchment runoff, lake level, redox conditions, grain size, organic matter, storms/extreme events, and trophic state, respectively. The lowest sedimentation rate, lake level, runoff values, highest trophic state and grain size were recorded between 1360–1800 CE, assigned to the Little Ice Age (LIA), under low humidity conditions related to the weakening of the South American Low-Level Jet (SALLJ). Subsequently, the highest sedimentation rate values, runoff and lake level were recorded up to the present. Concomitant lowest trophic state conditions were inferred and interpreted as dilution processes associated with higher lake levels. This stage was assigned to the onset of the Current Warm Period (CWP), which was characterized by higher humidity conditions leading to the highest sedimentation rate, lake level and runoff values after 1980 CE, associated with the noticeable increase in rainfall during “1970´s climatic shift”. By performing time series analyses, we determined centennial, multi-decadal, decadal, and inter-annual cyclicity in lake level related to the hydroclimatic variability. Furthermore, a high significant positive/negative Spearman correlation was observed between runoff and lake level/trophic state proxies and the El Niño Southern Oscillation (ENSO) reconstruction. ENSO modulates both long and short-term frequency of SALLJ, leading to an increase in rainfall during positive phases, which determined high lake level and runoff and a decreased trophic state due to dilution processes. The reconstructed hydrological variability herein is synchronic with other SESA lacustrine systems and the increased Rio de la Plata discharge, indicating similar long-term limnological responses to the regional climatic patterns.