There is widespread evidence for a reduction in biomass of tertiary consumers such as large predatory fish in lowland rivers. These declines are caused by a myriad of factors such as overfishing, habitat loss and fragmentation, declining water quality and alterations to spawning cues. Recently research has also emphasized the role of altered food-webs and changes in energy production as factors that may limit the current carrying capacity of higher consumers in these systems. Here we present a novel ecosystem approach to quantifying the effects of altered hydrology and altered food-web structure on the carrying capacity of large-bodied native fish in the Murray River, southeastern Australia. We combine estimates of current and historical primary production with current and historic food-webs to estimate energy available to support native fish species such as Murray cod and golden perch. Our results suggest firstly that river regulation and food-web changes have reduced energy fluxes to these native tertiary consumers by roughly 70% relative to historic levels, due to reduced production and the presence of trophic dead ends (notably carp). Secondly, both limitations will need to be addressed contemporaneously if carrying capacity of native fish is to be effectively increased.