Artificial water channels are synthetic molecules that aim to mimic the structural and functional features of biological water channels (aquaporins). Here we report on a cluster-forming organic nanoarchitecture, peptide-appended hybridarene (PAH), as a new class of artificial water channels. Fluorescence experiments and simulations demonstrated that PAHs can form, through lateral diffusion, clusters in lipid membranes that provide synergistic membrane-spanning paths for rapid and selective water permeation through water-wire networks. Quantitative transport studies revealed that PAHs can transport >109 water molecules per second per molecule, which is comparable to aquaporin water channels. The performance of these channels exceeds the upper bound limit of current desalination membranes by a factor of ~104, as illustrated by the water/NaCl permeability–selectivity trade-off curve. PAH’s unique properties of a high water/solute permselectivity via cooperative water-wire formation could usher in an alternative design paradigm for permeable membrane materials in separations, energy production, and barrier applications.