This study presents the long-term evolution of two floodplains lakes (San Juana and Barbacoas) of the Magdalena River in Colombia with varying degree of connectivity to the River and with different responses to climate events (i.e., extreme floods and droughts). Historical limnological changes were identified through a multi-proxy-based reconstruction including diatoms, sedimentation, and sediment geochemistry, while historical climatic changes were derived from the application of the Standardised Precipitation-Evapotranspiration Index. The main gradients in climatic and limnological change were assessed via multivariate analysis and generalized additive models. The reconstruction of the more isolated San Juana Lake spanned the last c. 500 years. Between c. 1620-1750 CE riverine-flooded conditions prevailed as indicated by high detrital input, reductive conditions, and dominance of planktonic diatoms. Since the early-1800s, the riverine meander became disconnected, conveying into a marsh-like environment rich in aerophil diatoms and organic matter. The current lake was then formed around the mid-1960s with a diverse lake diatom flora including benthic and planktonic diatoms, and more oxygenated waters under a gradual increase in sedimentation and nutrients. The reconstruction for Barbacoas Lake, a waterbody directly connected to the Magdalena River, spanned the last 60 years and showed alternating riverine-wetland-lake conditions in response to varying ENSO conditions. Wet periods were dominated by planktonic and benthic diatoms, while aerophil diatom species prevailed during dry periods; during the two intense ENSO periods of 1987 and 1992, the lake almost desiccated and sedimentation rates spiked. A gradual increase in sedimentation rates post-2000, suggest that other factors rather than climate are also influencing sediment deposition in the lake. We propose that hydrological connectivity to the Magdalena River is a main factor controlling lake long-term responses to human pressures, where highly-connected lakes respond more acutely to ENSO events while isolated lakes are more sensitive to local land-use changes.