Sweetpotato (Ipomoea batatas [L.] Lam) is an important starch crop that ensures food and nutrition security in the era of climate change. Sweetpotato is tolerant to environmental stresses such as drought, high temperature, and high salt, and there�fore, is well adapted to marginal lands; however, it is relatively vulnerable to fooding stress, which severely reduces its yield and commercial value. To understand the fooding stress response of sweetpotato, we performed comparative transcriptome analysis of the leaves of two sweetpotato cultivars with contrasting fooding stress tolerance levels: Yeonjami (YJM; food�ing tolerant) and Jeonmi (JM; fooding sensitive). Both cultivars were partially submerged in water for 0, 0.5, and 3 days. RNA-seq data of both cultivars revealed 14,229 diferentially expressed genes (DEGs), which were categorized into seven clusters and six groups, based on the expression pattern of co-expressed DEGs and expression duration of DEGs, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DEGs of distinguishing functions between the two cultivars were involved in plant hormone signaling, carbohydrate transport, and mitogen-activated protein kinase (MAPK) signaling. Based on these results, we predict that YJM promotes adventitious growth, whereas JM exhibits shoot elongation under fooding stress. The expression levels of several key candidate genes involved in fooding tolerance correlated well with the comparative transcriptomics data. Overall, this study provides further insights into the molecular mechanism of fooding stress response in sweetpotato, and reveals candidate genes that could be used for developing new fooding tolerant sweetpotato cultivars.