The time series of landings in the Venice Lagoon from 1945 to 2001 were analysed with the aim of explaining the ecosystem changes occurred. The comparative analysis of the total landings and mean Trophic Level (mTL) time series allowed to identify four different stages in the lagoon ecosystem. The first period, from 1945 to 1973, was characterised by increasing trends in the landings and their mTL. The second one, from 1974 to 1989, showed a decrease in the landings but still an increase in the mTL. The third period, from 1990 to 1998, had again a positive trend in the landings, but the mTL showed a sharp decline. After 1998, a slight decreasing trend in both mTL and landings was observed: the analyses of the artisanal fishery landings only date back to 1995 this effect. The presence of four distinct periods was also confirmed by the analysis of the trends of other indices estimated using landings data: the Fishing in Balance index (FiB), the Trophic Efficiency (TE) and the Pelagic on Demersal landings ratio (P/D). In the first period, the increasing fishing pressure, along with no evidence of ecosystem crisis, suggested that an increased nutrient discharge was supporting it; analogously, the bottom-up effects had driven the dynamics of the ecosystem also in the second period, when the decrease in nutrient loads caused a shift of the primary producers from planktonic to macrobenthic. The spreading of the Manila clam, a non-native species, and the development of its massive mechanical exploitation have been the main forces driving the ecosystem during the third period, for which, however, no signs of crises were detected. The fourth period showed evidence of the ''fishing down the food web'' effect. Possible causes of such an effect were investigated and allowed us to conclude that not overfishing, but the effects of mechanical harvesting of the Manila clam had caused relevant impacts on habitat and benthic communities, concluding that the present level of exploitation of the stock of Manila clam is not sustainable in the long term. Our findings were also compared with the general evolution of enclosed seas, subjected to high nutrient loads, fishing pressure and invasion by non-native species. D