<p>Precise and selective separation of target solutes from complex mixtures remains a critical yet challenging goal in industrial separation processes. Conventional membranes typically excel at separating either cations or anions but struggle to differentiate both simultaneously. In this study, we develop covalent organic framework (COF) membranes with vertically asymmetric charge distributions, fabricated via interfacial polymerization followed by nanosheet casting. These membranes exhibit pronounced ionic current rectification. Under single-salt conditions, the optimal membrane achieves exceptional selectivity values of H⁺/Mg²⁺ = 702 and NO₃⁻/PO₄³⁻ = 201. Remarkably, selectivity improves further in multicomponent systems. In an eight-component acid/salt mixture, the membrane demonstrates separation ratios of NO₃⁻/PO₄³⁻ = 380, NO₃⁻/SO₄²⁻ = 234, NO₃⁻/Cl⁻ = 11, H⁺/Li⁺ = 698, H⁺/Na⁺ = 1120, H⁺/K⁺ = 525, and H⁺/Mg²⁺ = 17182, maintaining stability for a continuous run for at least 216 h. This work introduces a robust membrane design strategy for highly selective solute separation from complex mixtures, offering valuable advancements for sustainable chemical recovery technologies.</p>