Sweetpotato (Ipomoea batatas [L.] Lam) is considered an economically important crop worldwide and is used as a source of food, feed, and biomaterials. However, its origin in tropical regions makes it vulnerable to chilling injury during postharvest storage at low temperature. To gain further insight into the molecular mechanism of chilling response, we performed comparative transcriptome analysis of two sweetpotato lines, Xushu 15-1 and Xushu 15-4, with high and low cold storage ability, respectively. Tuberous roots of these lines were stored at 4 °C for 0, 2, and 6 weeks. RNA-Seq data of both lines were de novo assembled, producing 27,636 unigenes with a N50 value of 1204 bp. A total of 525 differentially expressed genes (DEGs) were identified and categorized into six clusters. Genes with higher expression in Xushu 15-1 than in Xushu 15-4 significantly increased in number over time during low temperature storage. Functional annotation of DEGs using KEGG enrichment analysis showed that these DEGs were involved in carbohydrate metabolism, ribosome, protein processing in endoplasmic reticulum, plant-pathogen interaction, and plant hormone signal transduction. Several key candidate genes involved in KEGG pathways were selected and discussed further. The results of this study enhance our understanding of the complex mechanisms involved in low temperature tolerance in sweetpotato during storage and provide a set of candidate genes for the development of new varieties with improved cold storage ability.