Background: Taraxacum antungense Kitag., a perennial herb belonging to the genus Taraxacum in the family Asteraceae, has been traditionally used as a medicinal plant and is rich in bioactive constituents, including flavonoids and phenolic acids. Previous studies have demonstrated that Taraxacum-derived compounds possess antioxidant, anti-inflammatory, and antitumor activities. However, the anti-melanoma effects and potential cellular mechanisms of flavonoid-enriched extract from T. antungense remain largely unexplored. This study aimed to investigate the anti-melanoma effects of flavonoid-enriched extract from T. antungense and explore the potential mechanisms by integrating phytochemical analysis, network pharmacology, molecular docking, and experimental validation. Methods: Flavonoids in the flowers, leaves, and roots of T. antungense were characterized by UPLC-ESI-MS/MS. Network pharmacology was used to predict candidate bioactive constituents, potential anti-melanoma targets, and associated signaling pathways, and molecular docking was performed to assess predicted ligand–target interactions. The anti-melanoma activity of the flavonoid-enriched extract was evaluated using cell viability, Live/Dead staining, apoptosis, and mitochondrial membrane potential assays. Results: A total of 16 flavonoids were identified across the different organs of T. antungense, with 12 detected in the flowers, 11 in the leaves, and 12 in the roots. Network pharmacology analysis identified 172 potential anti-melanoma targets, with 17 predicted core targets including AKT1, EGFR, BCL2, PTGS2, CDK2, and GSK3B. Enrichment analysis suggested that these targets were mainly associated with cancer-related pathways and apoptosis-related biological processes. Molecular docking suggested favorable predicted interactions between candidate flavonoids (chrysin, luteolin, quercetin, apigenin, and kaempferide) and predicted core targets. In vitro experiments showed that flavonoid-enriched extract from T. antungense inhibited melanoma cell viability in a concentration-dependent manner, induced apoptosis, and induced mitochondrial membrane potential disruption. Conclusions: Our study demonstrates that flavonoid-enriched extract from T. antungense exerts anti-melanoma effects by suppressing melanoma cell viability and promoting apoptosis accompanied by mitochondrial membrane potential disruption. Network pharmacology and molecular docking further suggest that multiple targets and signaling pathways may contribute to these effects.