Electrochemical water splitting is a critical energy conversion process for producing clean and sustainable hydrogen; this process relies on low-cost, highly active, and durable oxygen evolution reaction/hydrogen evolution reaction electrocatalysts. Metal cations (including transition metal and noble metal cations), particularly high-valence metal cations that show high catalytic activity and can serve as the main active sites in electrochemical processes, have received special attention for developing advanced electrocatalysts. In this review, heterogenous electrocatalyst design strategies based on high-valence metal sites are presented, and associated materials designed for water splitting are summarized. In the discussion, emphasis is given to high-valence metal sites combined with the modulation of the phase/electronic/defect structure and strategies of performance improvement. Specifically, the importance of using advanced in situ and operando techniques to track the real high-valence metal-based active sites during the electrochemical process is highlighted. Remaining challenges and future research directions are also proposed. It is expected that this comprehensive discussion of electrocatalysts containing high-valence metal sites can be instructive to further explore advanced electrocatalysts for water splitting and other energy-related reactions.