Despite growing recognition of the importance of a natural flow regime in river-floodplain systems, researchers struggle to quantify ecosystem responses to altered hydrological regimes. How do frequency, timing, and duration of inundation affect fundamental ecosystem processes such as leaf litter decomposition? Along the semi-natural Tagliamento River corridor, located in northeastern Italy, we employed in situ experiments to separate effects of different inundation components on breakdown rates of black poplar (Populus nigra). We used a litter-bag method with two different mesh sizes to investigate how fungi and macroinvertebrates influence leaf breakdown rates. Ten treatments, each representing a specific combination of duration and frequency of inundation, were deployed in two seasons (summer, winter) to mimic complex inundation patterns. After 30 days of exposure, mean percentage of remaining leaf litter (ash free dry mass) ranged between 51% (permanent wet) and 88% (permanent dry). Leaf breakdown was significantly faster in winter than in summer. Duration of inundation was the main inundation component that controlled leaf breakdown rates. Leaf-shredding macroinvertebrates played only a role in the permanent wet treatment. Fungal parameters explained the faster leaf breakdown in winter. Our study suggests that modifications of the inundation regime will directly modify established decomposition processes. Factors reducing duration of inundation will decelerate leaf breakdown rates, whereas a decrease in flow variation will reduce leaf breakdown heterogeneity.