The antifouling properties of an equiatomic CoCrFeMnNi high-entropy alloy were investigated using Ulva fasciata (green alga) spores. The alloy exhibits antifouling properties superior to those of 304 stainless steel. The microstructural factors affecting antifouling properties were comprehensively studied. The hydrophilic nature of the alloy is not preferred by spores, which showed a lower rate of spore settlement, leading to enhanced antifouling properties. This HEA with superior antifouling properties is anticipated to be a candidate material of interest for use in marine industries.