Rice production in the Tonle Sap basin is one of the main drivers for economic and social development in Cambodia. The Tonle Sap basin has experienced many different forms of disasters while more attention has been drawn to drought disaster. The objective of this study is to assess the impacts of drought on agriculture and food security through a case study of the Baribo basin, a sub-basin of Tonle Sap basin, Cambodia. Ground observations and satellite-based products were used for drought assessment from 1985 to 2008 which was the period with relatively good data quality. The Standardized Precipitation Index (SPI) and Standard Vegetation Index (SVI) were selected for meteorological and agricultural droughts assessment, correspondingly. Both SPI and SVI consistently suggested that drought is a major natural hazard causing food insecurity in the target basin. The highest drought intensity (DI) and severity (DS) occurred between 1993-1994 and the longest drought duration (DD) occurred between 2002 and 2006. The most severe damage to rice production was in 2004, affecting about 46% of the total cultivated area. The analysis showed that drought duration had a strong relationship with the affected area growing rice as well as food insecurity in the Tonle Sap basin.