The major regional molluscan faunal turnover in the Plio-Pleistocene of the Tropical Western Atlantic has been attributed to drops in temperature or primary productivity, but without considering how taxa with widely differing ecologies might vary in relative susceptibilities to extinction or speciation. To discriminate between the two causal hypotheses we compiled molluscan life-habits and trophic composition data from 463 quantitative collections newly made by the Panama Paleontology Project. These bulk-sampled collections extend through 12Ma of dominantly shallow shelf deposition from the southwestern Caribbean, including comparable, time-averaged, dredged Recent collections. Analysis of bivalve feeding and life habits and gastropod feeding show shelf ecosystems to have altered markedly in trophic structure since the Late Pliocene. Massive cross-habitat declines in abundance, but not diversity, of predatory snails and suspension-feeding clams are consistent with a macroecological transition from heterotrophic and nutrient-rich to more phototrophic and nutrient-poor ecosystems in which reef-dwellers (e.g., cowries and worm-snails) became common. In contrast, all other ecological life-habits remained remarkably stable. These food-web changes provide the strongest support for the hypothesis that declining regional nutrient-supply associated with oceanographic changes - consequent upon Isthmian uplift - had an increasing impact on regional macroecology, culminating in a faunal turnover at 2Ma. Although the timing of turnover and origin of the 'modern Caribbean fauna' is similar, the detailed diversity dynamics of clams and snails, and reef corals are distinct.