Abstract: Synthesizing catalysts with multiple single-metal atoms remains challenging. We introduce high-entropy single-atom catalysts (HESACs) co-coordinated with six elements from a FeRuPtNiCoPd high-entropy alloy (HEA) on graphene oxide supports (HESAC–HEA/GO) via single-pot pulsed laser irradiation in liquids (PLIL). This method leverages tailored surface composition and diverse active sites for electrochemical overall water splitting (OWS) across a wide pH range. The synergistic interactions in high-entropy systems and rapid photoreduction of Fe²⁺ via PLIL enhance nuclei generation and active sites compared to Fe³⁺, achieving high HER in 0.5 M H₂SO₄ with η of 49 mV at 10 mA/cm², and record-high OER in 1.0 M KOH with η of 398 mV. Optimized HESAC–HEA/GO–Fe²⁺ shows exceptional OWS performance with lower cell voltage compared to HESACC–HEA/GO–Fe³⁺ and Pt/C. This study offers a robust pathway for fabricating versatile catalysts and facilitates mechanistic insights through in situ Raman and density functional theory analyses.