Proxy reconstructions of precipitation from central India, north-central China, and southern Vietnam reveal a series of monsoon droughts during the mid 14th–15th centuries that each lasted for several years to decades. These monsoon megadroughts have no analog during the instrumental period. They occurred in the context of widespread thermal and hydrologic climate anomalies marking the onset of the Little Ice Age (LIA) and appear to have played a major role in shaping significant regional societal changes at that time. New tree ring-width based reconstructions of monsoon variability suggest episodic and widespread reoccurrences of monsoon megadroughts continued throughout the LIA. Although the El-Niño Southern Oscillation (ENSO) plays an important role in monsoon variability, there is no conclusive evidence to suggest that these megadroughts were associated with anomalous sea surface temperature anomalies that were solely the result of ENSO-like variability in the tropical Pacific. Instead, the causative mechanisms of these megadroughts may reside in protracted changes in the synoptic-scale monsoon climatology of the Indian Ocean. Today, the intra-seasonal monsoon variability is dominated by ‘active’ and the ‘break’ spells – two distinct oscillatory modes of monsoon that have radically different synoptic scale circulation and precipitation patterns. We suggest that protracted locking of the monsoon into the “break-dominated” mode – a mode that favors reduced precipitation over the Indian sub-continent and SE Asia and enhanced precipitation over the equatorial Indian Ocean, may have caused these exceptional droughts. Impetus for periodic locking of the monsoon into this mode may have been provided by cooler temperatures at the extratropical latitudes in the Northern Hemisphere which forced the mean position of the Inter-Tropical Convergence Zone (ITCZ) further southward in the Indian Ocean.