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Sweet potato, commonly planted in Southeast Asia and South America with abundant rainfall, often suffers from waterlogging. The aerenchyma formation in roots is an effective way for plants to facilitate gas exchange. In the present study, tolerant and sensitive varieties, respectively, designated NC1 and C211, were evaluated under water oxygen content at 2.0 mg·L−1 (hypoxia treatment) and 8.0 mg·L−1 (control). The results showed that NC1 variety has a relatively higher root growth rate under low oxygen condition. In NC1 plants, aerenchyma was observed in the mid‐section of the main adventitious root and spread to the proximal and distal ends, forming a complete channel in the cortex. However, in C211 plants, the aerenchyma occurred relatively later and could not turn into a whole channel. Ethylene synthesis‐related (ACS1, ACS4, ACS5, etc.) and signal transduction‐related (ETR1, ERS1, EIN2, etc.) genes were upregulated in the NC1 plants and led to changes in the reactive oxygen species‐related genes (RBOHA, SOD, CAT, etc.) and enzyme activities. It was found that programmed cell death was induced by H2O2 accumulation. A regulatory model of lysigenous aerenchyma formation in the root of sweet potato was constructed. Our study enriches the understanding of the mechanisms of the aerenchyma formation in plants. [ABSTRACT FROM AUTHOR]