Floods are amongst the most dangerous natural hazards in terms of economic damage. Whilst a growing number of studies have examined how river floods are influenced by climate change, the role of natural modes of interannual climate variability remains poorly understood. We present the first global assessment of the influence of El Niño–Southern Oscillation (ENSO) on annual river floods, defined here as the peak daily discharge in a given year. The analysis was carried out by simulating daily gridded discharges using the WaterGAP model (Water – a Global Assessment and Prognosis), and examining statistical relationships between these discharges and ENSO indices. We found that, over the period 1958–2000, ENSO exerted a significant influence on annual floods in river basins covering over a third of the world's land surface, and that its influence on annual floods has been much greater than its influence on average flows. We show that there are more areas in which annual floods intensify with La Niña and decline with El Niño than vice versa. However, we also found that in many regions the strength of the relationships between ENSO and annual floods have been non-stationary, with either strengthening or weakening trends during the study period. We discuss the implications of these findings for science and management. Given the strong relationships between ENSO and annual floods, we suggest that more research is needed to assess relationships between ENSO and flood impacts (e.g. loss of lives or economic damage). Moreover, we suggest that in those regions where useful relationships exist, this information could be combined with ongoing advances in ENSO prediction research, in order to provide year-to-year probabilistic flood risk forecasts.