Severe drought over the past three years (1998–2001), in combination with the effects of protracted sociopolitical disruption, has led to widespread famine affecting over 60 million people in central and southwest (CSW) Asia. Here both a regional and a large-scale mode of climate variability are documented that, together, suggest a possible forcing mechanism for the drought. During the boreal cold season, an inverse relationship exists between precipitation anomalies in the eastern Indian Ocean and CSW Asia. Suppression of precipitation over CSW Asia is consistent with interaction between local synoptic storms and wave energy generated by enhanced tropical rainfall in the eastern Indian Ocean. This regional out-of-phase precipitation relationship is related to large-scale climate variability through a subset of El Niño–Southern Oscillation (ENSO) events characterized by an enhanced signal in the warm pool region of the western Pacific Ocean. Both the prolonged duration of the 1998–2001 cold phase ENSO (La Niña) event and unusually warm ocean waters in the western Pacific appear to contribute to the severity of the drought.