Drought is one of the most important abiotic stresses that impair sesame (Sesamum indicum L.) productivity mainly when it occurs at flowering stage. However up to now, very few studies have attempted to investigate the molecular responses of sesame to drought stress. In this experiment, two genotypes having contrasting responses to drought (tolerant and sensitive) were submitted to progressive drought followed by recovering stage at flowering stage. RNAs were isolated from roots of plants before drought stress, at 3-time points during progressive drought, after rewatering, and sequenced using Illumina HiSeq 4000 platform. These RNA-Seq resources (BioSample IDs: SAMN06130606 and SAMN06130607) provided an opportunity to elucidate the molecular responses of sesame to drought and find out some candidate genes for drought tolerance improvement.