Melanoma, which features high metastasis and high lethality, is one of the toughest tumors to treat. Chrysin, which is rich in various plants, has shown a great inhibitory effect on melanoma proliferation. Here, we evaluated the metastasis suppressive effect of chrysin on melanoma in vivo and in vitro. In vitro, chrysin effectively inhibited ankios resistance from 5 μM cell migration, invasion from 10 μM, and tube formation capacity of melanoma cells from 20 μM. We discovered that chrysin interfered with the mesenchymal–epithelial transition via regulating FOXM1/β-catenin signaling, as the expression of key regulatory factors was downregulated by chrysin treatment, and overexpression of FOXM1 will attenuate the antimetastasis effect of chrysin. We also tested chrysin on lung colonization in melanoma metastasis, where we found fewer tumors were formed in the lungs of chrysin-treated mice. In addition, the expression of FOXM1 was also downregulated by chrysin in vivo. Collectively, our findings suggested the ability of chrysin treatment to lower the metastatic rate of melanoma through regulating FOXM1/β-catenin signaling, indicating the application potential of chrysin for melanoma therapy.