Compared with freshwater splitting, seawater electrolysis has more spaces to be explored, which is primarily attributed to the additional critical catalytic challenges of the competition between anodic oxygen evolution reaction (OER) and chlorine chemistry, deep corrosion, and site blocking due to the presence of chloride ions and insoluble particulate in seawater. However, if direct seawater electrolysis can be realized, it would revolutionize the energy and environmental sectors. In this review, the current effective strategies are summarized, including electronic modulation, oxygen vacancies creation, amorphous and porous structure design, corrosion-resistant passive layer decoration, and creating strong catalyst-support interactions. The review also provides insights for seawater electrolysis on rational design of the OER catalyst with high selectivity, activity, corrosion resistance, chemical, and mechanical durability. Beyond the progress made to date, a perspective in the fabrication of high-performance anodes for direct seawater electrolysis is also proposed. Collectively, this review will shed light on the rational design of a viable anode for massive and sustainable hydrogen fuel production from immense seawater.