Key message <p>MT mitigates Cd toxicity by enhancing photosystem and antioxidant system activities, and related gene expression in GCC. NAC, HSF, and MYB-related families may play key roles in MT-induced Cd tolerance.</p> Abstract <p>Cadmium (Cd), a toxic heavy metal non-essential to plants, has detrimental impacts on both the environment and human health. Melatonin (MT) plays an important protective role in plants against stresses such as heavy metal toxicity. However, the detailed mechanism underlying MT alleviating Cd toxicity remains unclear in ground-cover chrysanthemum (<i>Chrysanthemum morifolium</i> Ramat., GCC). GCC seedlings were pre-treated with MT solution (150 μM) via foliar spraying and subsequently grown under Cd stress, after which the growth, physiological, and transcriptomic responses of the plant were investigated. The results demonstrated that MT pre-treatment inhibited the Cd-induced chlorophyll degradation in GCC seedlings, while it enhanced chlorophyll synthesis and related gene expression by promoting electron transfer efficiency and maintaining the integrity of the oxygen-evolving complex in photosynthesis. Furthermore, MT + Cd treatment upregulated 11 photosystem I (PSI), 13 PSII, eight light-harvesting complex I (LHCI), and 20 LHCII-related genes as compared with Cd treatment alone. MT also alleviated oxidative stress and boosted antioxidant capacity by conserving the activities and gene expression levels of superoxide dismutase, peroxidase, and key enzymes in the ascorbate–glutathione cycle and thioredoxin–peroxiredoxin pathway. In addition, MT reduced the generation rate of O₂^·– by 27.64%, malondialdehyde by 68.36%, and H₂O₂ by 44.97%, alleviating the Cd-induced damage. Weighted gene co-expression network analysis provided additional evidence that MT improved GCC tolerance to Cd by modulating the expression of transcription factors (<i>e.g.</i>, NAC, HSF, and MYB-related families) related to abiotic stress.</p> Graphical Abstract <p></p>