Rational modification of the chemical components of the metal− organic framework (MOF) is one of the most promising and challenging strategies to alternate noble metals in the electrochemical water-splitting field. Multimetallic MOFs have emerged as excellent materials for several applications; however, it remains a significant challenge to synthesize and characterize these materials. In this work, we report a facile approach to synthesizing a series of multimetallic MOF nanosheet-assembled hierarchical flower-like morphologies as highly active and durable electrocatalysts for natural seawater electrolysis. Simultaneously, their three-dimensional hierarchical nanostructures and multimetallic components can provide abundant active sites, improve intrinsic catalytic activity, and facilitate electron transfer. Consequently, the obtained RhCoNi-MOF exhibits overpotentials as low as 40, 48, and 50 mV at 10 mA cm −2 in alkaline freshwater, alkaline simulated seawater, and alkaline natural seawater. In natural seawater, the RhCoNi-MOF also offers an outstanding performance comparable to Pt/C. Impressively, a two-electrode overall seawater electrolysis device using RhCoNi-MOF as a bifunctional catalyst requires a voltage of 1.52 V at 10 mA cm −2 and can stably maintain over 80 h. The density functional theory calculation reveals that the superior electrocatalytic activity of the RhCoNi-MOF can be attributed to the synergistic effects of introducing Co and Rh metal ions.