<p>The lifespan of reverse osmosis (RO) membranes is only several months when used for industrial wastewater treatment rather than several years for seawater desalination, dramatically increasing the maintenance cost of RO. Here, to improve the separation and anti-fouling performance and thus increase the lifespan of RO membranes, we developed a creative strategy to methylate RO membranes via grafting gaseous dimethylamine molecules onto polyamide (PA) of RO membrane during interfacial polymerization. The dimethylamine-grafted RO membrane achieved a high water permeance of 3.84 l m⁻² h⁻¹ bar⁻¹ and a high NaCl rejection of 99.05% and exhibited unprecedented anti-fouling performance against small organic charged foulants, surpassing the upper-bound threshold of the other reported anti-fouling membranes and the well-known commercial anti-fouling RO membrane (DuPont FilmTec Fortilife CR100). Both experimental results and molecular dynamics simulation findings illustrate that the methylated PA has a lower absorption energy with small charged organic foulants than the pristine PA, which alleviates the foulantsʼ absorption with a lower areal density and a looser packing, and a much shallower penetration depth inside PA. Our work suggests that avoiding penetration of foulants inside PA and preventing pore blocking of PA by foulants are essential to improve the fouling resistance of RO membranes. This work contributes a new outlook on the RO membrane-fouling mechanism from the molecular levels using molecular dynamics simulation and also develops a simple and effective methylation approach to enhance the RO membrane-fouling resistance towards small charged foulants.</p>