Leafy sweet potato is rich in caffeoylquinic acids (CQAs), including monoCQAs and diCQAs, which play important roles in plant resistance to environmental stresses. However, knowledge about the genes responsible for the accumulation of CQAs is limited. Studies have reported the involvement of glutathione S-transferase (GST) genes in the metabolism of various plant secondary compounds; yet, the mechanism of CQA-related GST proteins is not well understood. In this study, two sweet potato GST genes, i.e., itb01g35330 (IbGSTTCHQD) and itb09g30700 (IbGSTT), were selected from our transcriptome database and investigated for their correlation with the accumulation of CQAs, as they exhibited secondary metabolism functions based on gene ontology classification. The two genes were cloned from the leafy sweet potato varieties EC16 and FS7-6. Sequence alignment of the coding regions of these genes from the two varieties revealed slight mutations in the amino acid sequences. Besides, the expression of the two genes was higher in the EC16 compared to the FS7-6 variety, which corresponds to the accumulated amounts of CQAs in both varieties. The amplified IbGST sequences from the EC16 variety were further transformed into Agrobacterium tumefaciens and subsequently introduced into Nicotiana benthamiana and Nicotiana tabacum for transient expression and transgenic transformation, respectively. Gene expression profiling in both transformation approaches revealed significant increases in IbGST transcripts in transformed leaves, resulting in an enhanced accumulation of monoCQAs compared to the wild-types. However, no significant change was observed in the level of diCQAs. In addition, the IbGSTs responded positively to salinity and oxidative stresses. Our findings suggested that IbGSTTCHQD and IbGSTT genes might be involved in the accumulation of monoCQAs in leafy sweet potato.