<p>Lithium is critical for energy storage and global electrification, yet rising demand and limited reserves highlight the urgent need for efficient, sustainable lithium extraction technologies from unconventional water sources. A persistent challenge is separating lithium from the chemically similar sodium and potassium ions. Inspired by sodium–potassium cotransporter proteins, which regulate ion transport through selective pores, we prepared a metal–organic framework (MOF)-based ion-selective glass composite (ISGC) membrane via melt quenching of glassable zeolitic imidazolate framework 62 (ZIF-62) with thermally stable ZIF-8. The resulting confined sub-nanometre channels discriminated monovalent cations and exhibited high selectivity through coupled dehydration–rehydration effects and weak ion–MOF interactions, as confirmed by molecular dynamics simulations. In binary mixtures, the a_g[(ZIF-62)_0.7(ZIF-8)_0.3] membranes achieved K⁺/Li⁺ and Na⁺/Li⁺ selectivities of 185 and 53.3 at a 1:1 feed ratio. Notably, even at a 10:1 ratio (excess of K⁺), the K⁺/Li⁺ selectivity remained ~10. In multi-ion brines, selectivity was further enhanced, reaching 410 for K⁺/Li⁺ and 80 for Na⁺/Li⁺. Notably, we scaled up laboratory membranes into robust disc–tube modules compatible with crossflow operation, which enriched lithium from synthetic salt-lake brines to 64.6 g l⁻¹ and enabled direct precipitation of battery-grade Li₂CO₃ at an energy input of only 1.02 kWh kg⁻¹. By bridging molecular-level ion discrimination with scalable engineering, this work positions MOF-ISGC as a transformative platform for sustainable lithium recovery and selective ion separations in water and energy systems.</p>