Human interactions with rivers commonly lead to biotic homogenization and suppression of indigenous biodiversity. Two pervasive human influences on rivers are flow regulation through dams and introductions of non-native species. Although combined effects of these stressors have been examined in rivers downstream of large dams, understanding of how disrupted flow regime and novel communities influence food web structure and function within spatially heterogeneous floodplains more distant from dams is lacking. We studied food-webs of a floodplain habitat mosaic of the Snake River, Idaho, USA, characterized by diminished flooding and prevalent non-native species. At five sites encompassing longitudinal and lateral dimensions of the floodplain, we estimated secondary production of invertebrates and fishes, trophic basis of production of fishes, and constructed organic matter flow food webs. Fish communities consumed ~70% more benthic prey production in habitats scoured by groundwater upwelling and flood-water connectivity with the main river compared to un-scoured sites dominated by fine sediments. However, in bed-scoured springbrooks, ~20% of total fish consumption was of relatively indigestible algae and plants by introduced trout, and invasive New Zealand mudsnails (Potamopyrgus antipodarum), despite representing ~20% of benthic production, contributed only 2% of total consumption by fishes. Based on a “meta-food web” analysis, which sequentially aggregated and compared food webs at increasing levels of landscape complexity, introduced fishes contributed 2X more spatially repeated food-web links than indigenous fishes. Despite evidence of large-scale alteration of food webs, we also observed a natural capacity for seasonal dynamism in feeding interactions, which may be key for future resilience. Our findings suggest that river regulation and introduced species constrained material flow through floodplain-mosaic food webs, and introduced fishes dominated and homogenized the floodplain-scale food web. Thus, combinations of multiple management strategies, namely designing ecological flows and removing non-native species, are needed in order to promote native, riverine biodiversity.