An analysis of the variability of rainfall at 27 stations and run-off at 4 stations between 18°and 28°S in the Atacama Desert has been carried out. A diagonal boundary zone between summer-and winter-dominated areas is related to the provenance of the rainfall: Amazonia to the north and east, and Pacific moisture to the south. It is shown that winter rainfall tends to be higher during El Niño years, while heavy summer rainfall tends to be more common during La Niña. However, rather than the precipitation being directly controlled by El Niño-Southern Oscillation (ENSO), previous studies have shown that it is the regional synoptic conditions towards the source areas that largely control temporal precipitation variations, and these are in turn either facilitated or inhibited by ENSO. The spatio-temporal variability of precipitation leads to a complex hydrological regime. Perennial rivers in the north and central Atacama Desert tend to flood in summer, especially during La Niña conditions, from source to sea. Perennial rivers in the south tend to flood in summer, but as a result of melt from the previous years snowfall, especially during El Niño conditions, again from source to sea. However, while inland areas may also experience flooding of ephemeral rivers in summer associated with La Niña, coastal areas on the other hand experience winter flooding of ephemeral rivers associated with El Niño. Surface water flood events, and groundwater recharge events reported in the literature, are generally less frequent than ENSO events, confirming the requirement for specific synoptic conditions and making the use of averages unsound for present-day hydrological studies and water resource evaluations.