In this study, the anthropogenic contamination in Trasimeno lake (Central Italy) was investigated using three sediment cores of the last 150 years (Anthropocene) to identify the primary sources of pollutions and quantify the level of contaminant enrichment in the basin. To this aim, trace elements, polycyclic aromatic hydrocarbons, and lead isotope ratios have been determined at biannual resolution. The deeper parts of the sediment cores were used to estimate the local geochemical baseline, based on known statistical methods, and to determine the values of enrichment factors. Principal component analysis and factor analysis were exploited to associate chemical proxies to human-driven contamination processes. On these grounds it was possible to identify the timings and impacts of pre-world war industrial productions and more recent activities characteristic of the basin's surroundings, such as agriculture.