<p><span lang="EN-US">Solvent reverse osmosis is a pressure-driven</span><span lang="EN-US">, liquid-phase</span><span lang="EN-US"> process for separating solvent mixtures, offering </span><span lang="EN-US">a potential low-energy</span><span lang="EN-US"> alternative to thermal operations. Graphene oxide (GO) laminates provide tunable nanochannels to </span><span lang="EN-US">probe confined </span><span lang="EN-US">solvent transport, yet solvent–solvent separations remain underexplored due to solvation-induced structural instabilities and the small </span><span lang="EN-US">molecular sizes</span><span lang="EN-US">. Here we construct</span><span lang="EN-US"> solvent-stable,</span><span lang="EN-US"> supported GO nanochannel membranes </span><span lang="EN-US">that preserves integrity under pressurized solvents,</span><span lang="EN-US"> and tune interlayer confinement and surface polarity via controlled chemical reduction. Across 51 solvent systems and 5 distinct nanochannels, we demonstrate that separation is governed by coupled nanoconfinement and solvent affinity, where selective interfacial association can surpass simple size-exclusion expectations. Maximum permselectivity arises from balancing channel size with retained polarity, indicating that channel shrinking alone does not optimize performance. These findings identify channel surface chemistry as a key design factor for polarity-rich solvent systems and provide a framework for rationally tailoring nanochannels for complex solvent separations.</span></p>