Abstract Seawater electrolysis offers a sustainable route for hydrogen production but challenges, including sluggish water dissociation, chloride‐induced poisoning, and metal hydroxide precipitation. Combinations of 36 three cost‐effective host metals (Co, Ni, Cu) and twelve oxophilic dopants are screened to optimize alkaline hydrogen evolution reaction (HER) activity, stability, and seawater compatibility. Oxophilic dopants improve water dissociation and chloride resistance but may accelerate hydroxide accumulation. Computational screening identified Ni─V, Ni─Mo, and Co─V as top candidates. Subsequent experiments confirmed Ni 20 V exhibits superior HER activity, achieving 76 mV lower overpotential than Pt/C at 100 mA cm −2 in 1 m KOH. In the overall water splitting system, it retained excellent durability with only an 81 mV increase after 200 h. Moreover, Ni 20 V achieved a price activity of 801.2 A $ −1 at 1.9 V, which is nearly 1000 times higher than commercial Pt/C. This work advances cost‐effective, durable alternatives to Pt‐based HER catalysts for seawater electrolysis.