Globally, freshwater shortage is one of the most dangerous risks for society. Changing hydro-climatic and socioeconomic conditions have aggravated water scarcity over the past decades. A wide range of studies show that water scarcity will intensify in the future, as a result of both increased consumptive water use and, in some regions, climate change. Although it is well-known that El Niño-Southern Oscillation (ENSO) affects patterns of precipitation and drought at global and regional scales, little attention has yet been paid to the impacts of climate variability on water scarcity conditions, despite its importance for adaptation planning. Therefore, we present the first global-scale sensitivity assessment of water scarcity to ENSO, the most dominant signal of climate variability. We show that over the time period 1961-2010, both water availability and water scarcity conditions are significantly correlated with ENSO-driven climate variability over a large proportion of the global land area (> 28.1 %); an area inhabited by more than 31.4 % of the global population. We also found, however, that climate variability alone is often not enough to trigger the actual incidence of water scarcity events. The sensitivity of a region to water scarcity events, expressed in terms of land area or population exposed, is determined by both hydro-climatic and socioeconomic conditions. Currently, the population actually impacted by water scarcity events consists of 39.6 % (CTA: consumption-to-availability ratio) and 41.1 % (WCI: water crowding index) of the global population, whilst only 11.4 % (CTA) and 15.9 % (WCI) of the global population is at the same time living in areas sensitive to ENSO-driven climate variability. These results are contrasted, however, by differences in growth rates found under changing socioeconomic conditions, which are relatively high in regions exposed to water scarcity events. Given the correlations found between ENSO and water availability and scarcity conditions, and the relative developments of water scarcity impacts under changing socioeconomic conditions, we suggest that there is potential for ENSO-based adaptation and risk reduction that could be facilitated by more research on this emerging topic.