Waterlogging stress lowers yields in sesame (Sesamum indicum L.).A major component of water-logging stress is the lack of oxygen available to submerged tissues.Although the morphology and physiology of plants grown under anaerobic conditions have been studied in detail, limited work has been done to elucidate adaptations at the molecular level.To gain comprehensive insight into how sesame responds to hypoxia at the genome level, we performed gene expression profiling at two time points during a 36-h period following hypoxic treatment using a whole-genome RNA-Seq analysis.We identified sets of significantly positively and negatively expressed genes (induced and repressed, respectively) in response to hypoxia with distinct temporal profiles.The genes that were affected were associated with glycolysis, nitrogen metabolism, starch and sucrose metabolism and plant hormone signal transduction and indicated the upregulation of particular pathways (glycolysis/glycogenesis) in the Kyoto Encyclopedia of Genes and Genomes.Moreover, significant changes in the expression of genes were found for pathways including flavone and flavonol biosynthesis, steroid biosynthesis, photosynthesis, cysteine and methionine metabolism, glutathione metabolism, as well as phenylpropanoid biosynthesis, spliceosome, circadian rhythm.This study helps to elucidate the molecular mechanisms of waterlogging tolerance and provides a basis for the genetic engineering of sesame.