Fouling refers to the undesirable attachment of organic molecules and microorganisms to submerged surfaces. It is an obstacle to the purification of shale gas produced water and is currently without an effective solution due to the highly contaminated nature of produced water. Here, we demonstrate the direct vapor application of a robust zwitterionic coating to a variety of substrates. The coating remains unprecedentedly hydrophilic, smooth, and effectively antifouling in extremely high salinity solutions (with salt concentration of 200 000 ppm). The fouling resistance is assessed rapidly and quantitatively with a molecular force spectroscopy-based method and corroborated using quartz crystal microbalance system with dissipation monitoring. Grazing angle attenuated total reflectance Fourier transform infrared is used in combination with X-ray photoelectron spectroscopy, atomic force microscope, and in situ spectroscopic ellipsometry to lend insight into the underlying mechanism for the exceptional stability and effectiveness of the zwitterionic coating under high-salinity conditions. A unique coating architecture, where the surface is concentrated with mobile zwitterionic moieties while the bulk is cross-linked to enhance coating durability, was discovered to be the origin of its stable fouling resistance under high salinity. Combined with previously reported exceptional stability in highly oxidative environments and strong fouling resistance to oil and grease, the zwitterionic surface here has the potential to enable low-cost, membrane-based techniques for the purification of produced water and to eventually balance the favorable economics and the concerning environmental impacts of the hydraulic fracturing industry.