Historical trends of PCDD/Fs and PCBs from the year 1900 have been reconstructed for the Venice Lagoon area by using a fugacity-based dynamic multimedia model. A novel approach to estimate the inputs to the system was applied. Emissions to the lagoon were estimated by studying dated sediment cores taken from salt marshes located in the lagoon area. These cores have recently proven to be a suitable tool to reconstruct the temporal trends of atmospheric deposition of POPs. According to the model, concentrations of PCBs and PCDD/Fs in air and water reflect the trends of their production and usage, peaking during the 1960s. The peaks in the sediment were delayed by 5–40 years depending on the congener. Predicted concentrations are in good agreement with experimental results. The most important input parameters, identified by a sensitivity analysis, are the degradation constants, Kow, the Henry's law constant, vapour pressure, active sediment depth, sediment resuspension, and deposition rates, and water residence time in the lagoon.