Inspired by biological proteins, artificial water channels (AWCs) can be used to overcome the performances of traditional desalination membranes. Their rational incorporation in composite polyamide provides an example of biomimetic membranes applied under representative reverse osmosis desalination conditions with an intrinsically high water-to-salt permeability ratio. The hybrid polyamide presents larger voids and seamlessly incorporates I–quartet AWCs for highly selective transport of water. These biomimetic membranes can be easily scaled for industrial standards (>m2), provide 99.5% rejection of NaCl or 91.4% rejection of boron, with a water flux of 75 l m−2 h−1 at 65 bar and 35,000 ppm NaCl feed solution, representative of seawater desalination. This flux is more than 75% higher than that observed with current state-of-the-art membranes with equivalent solute rejection, translating into an equivalent reduction of the membrane area for the same water output and a roughly 12% reduction of the required energy for desalination.