Large river floodplains wetlands have complex food web structure and dynamics that supports significant ecosystem goods and services. However, increased river regulation and catchment modifications have profoundly interrupted the connectivity between the river and wetlands. The disruption in the connectivity has not only altered the natural flow of carbon and nutrients across the river network but also modified the movement of energy and nutrient masses from the base of the food web to the higher trophic levels. Climate change has amplified the conditions further. Until recently, studies have mostly focused on trophic dynamics of contemporary floodplain river systems, however, the context of carbon energy and nutrient mass flows in the food web over a longer time scale are rarely documented. Here, a new approach, an integration of paleoecology, modern and paleo-food web dynamics has been used for understanding the long-term change of wetland ecosystem and food web structure and dynamics of the floodplain wetlands of the two large river systems, River Murray (Australia) and Yangtze River (China). Abundances of subfossil cladcoeran zooplankton, stable isotopes of carbon and nitrogen in modern fish, modern Daphnia and modern sub-merged macrophytes, and subfossil Daphnia, and bulk sediment samples from Kings Billabong (River Murray) and Taihu Lake (Yangtze River) were analyzed. The results suggest that the ecosystems and food webs of floodplains wetlands of both river systems have transformed from a natural clear water phase to a more eutrophic, algal-dominated turbid water phase following river regulation during the mid-20th century. Over the period, such changes have modified the wetland littoral habitats with significant loss of submerged macrophytes followed by the nature of available food sources at the base of the food webs for primary consumers as indicated by rapid decrease in d13C with reciprocal increase in the d15N values of wetland biota. This study highlights the urgent need of the better management actions through a comprehensive understanding of the rapid change of food web structure and dynamics of regulated floodplains wetlands in large river systems of Australia and China.