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Compounds were isolated from <i>Ecklonia stolonifera</i> Okamura, a marine brown alga widely consumed as food. Among the isolated compounds, 974-A was demonstrated for the first time to be a potent competitive inhibitor of mushroom tyrosinase activity towards <span style="font-variant: small-caps;">l</span>-tyrosine and <span style="font-variant: small-caps;">l</span>-DOPA (IC₅₀ values = 1.57 &#177; 0.08 and 3.56 &#177; 0.22 &#181;M, respectively). Molecular docking simulations clarified that the hydroxyl residues of the isolated compounds formed hydrogen bonds with residues at the catalytic and allosteric sites of tyrosinase, while other residues participated in hydrophobic interactions. Moreover, 974-A, phlorofucofuroeckol-A and eckol reduced the cellular melanin content and tyrosinase activity, and downregulated the expression of melanogenesis enzymes including tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 in B16F10 melanoma cells. These compounds also effectively scavenged radicals at the cellular level. Thus, our results revealed that compounds isolated from <i>E. stolonifera</i> are potent tyrosinase inhibitors with potential applications in the cosmetic industry for treatment of hyperpigmentation and for the anti-browning effect in the agricultural field.