It has been well established that exogenous melatonin (MT) improves storage quality of many agricultural products. However, contrasting results have been reported in the regulation of MT with respect to several postharvest parameters, e.g., germination/sprouting and lignification, indicating that roles of MT may vary with plant species or storage environment. Previous studies mainly focus on above-ground organs including fruits, leaves, seedlings and flowers without addressing underground organs such as the storage root (SR) of sweetpotato (Ipomoea batatas). This study showed that spraying 0.5 mM MT solution improved postharvest quality of sweetpotato SRs during 40 d of storage at 15 °C. First, MT treatment inhibited SR sprouting by differentially regulating the content of germination-related hormones, i.e., increasing the content of ABA and JA but decreasing GA content. Second, MT reduced weight loss and lignification by inhibiting respiration as reflected by decreased respiration rate and hexose kinase activity. Third, MT treatment increased soluble sugar content by elevating the activity and expression of sucrose synthase (Sus) since the activities and expressions of invertases (CWIN, CIN and VIN) were inhibited by MT. Simultaneously, inhibited respiration by MT also contributed to increased content of soluble sugar by reducing their expenditure via glycolysis. Additionally, MT increased starch content by inhibiting β-amylase activity and possibly also by increasing Sus activity, which provides a substrate for starch biosynthesis. Finally, MT upregulated the activities of SOD, POD and CAT, which may improve storage quality of SRs by inhibiting senescence and lignification. This study provides an alternative option to maintain the storage quality of sweetpotato.