Mg-Al-Pb-Zn alloy is a typical anode material used for high-power seawater activated battery. The chemical composition of a series of Mg-Al-Pb-(Zn) alloys is optimized by a L9 orthogonal array test and the effects of alloying elements, such as aluminium, lead and zinc, on electrochemical properties are investigated through signal-to-noise ratio (S/N) analysis. Microstructure characterization and half-cell test demonstrate that the selected optimal Mg-6%Al-7%Pb-0.5%Zn (wt%) alloy is a good candidate as an anode material for seawater activated battery application due to its high discharge activity, negative discharge potential in large current densities and comparatively higher anode utilization efficiency. The prototype battery assembled with Mg-6%Al-7%Pb-0.5%Zn alloy as anode and AgCl as cathode reveals excellent discharge performance, reaching a superior specific energy of 155 Wh·kg−1.