Tropical floodplain lakes are increasingly impacted by human activities, yet their pathways of spatial and temporal degradation, particularly under varying hydrological connectivity regimes and climate change, remain poorly understood. This study examines surface-sediment samples and 210Pb-dated sediment cores from six floodplain lakes, representing a gradient in hydrological connectivity in the lower Magdalena River Basin, Colombia. We analysed temporal and spatial variations in several sediment biogeochemical indicators: the concentration and flux of nutrients, heavy metals, and organic matter (OM), and redox conditions, flooding and erosion. Multiple factor analysis (MFA) of surface-sediments identified redox conditions, OM, flooding, heavy metals and lake connectivity as the main contributors to spatial variability within- and between-lakes sediments, accounting for 48% of the total variation. Additionally, no clear distinction was found between littoral and open-water sediment characteristics. Isolated lakes sediments exhibited reductive conditions rich in OM and nutrients, whereas connected lakes sediments showed greater heavy metal enrichment and higher concentrations of coarse river-fed material. Generalised additive models identified significant changes in the biogeochemical indicators since the late 1800s, that accelerated post-1980s. Shifts in OM, erosion, flooding, redox conditions, land-cover change, heavy metals and climate were identified by MFA as the main drivers of change, explaining 60%-71% of the variation in the connected lakes and 53%-72% in the isolated lakes. Post-1980s, connected lakes transitioned from conditions of higher accumulation of OM and little erosion to higher accumulation of heavy metals and river-fed material. Conversely, isolated lakes, shifted from detrital-heavy metal-rich sediments to OM-, and nutrient-rich, reductive sediments. Sedimentation rates also surged post-1980s, particularly in highly connected lakes, from 0.14 ± 0.07 g cm² yr⁻¹ to 0.5 ± 0.5 g cm² yr⁻¹, with elevated fluxes of metals, OM and nutrients. These changes in sediment biogeochemistry align with deforestation, river regulation and prolonged dry periods, highlighting the complexities behind establishing reliable reference conditions for pollution assessments in large, human-impacted tropical river systems.