Membrane-based air humidification-dehumidification desalination (MHDD) is an emerging seawater desalination process that can be driven by low-grade, renewable energy sources; however, membrane fouling and wetting are key issues that hinder its practical application. In this study, a composite membrane using a hydrophobized MXene deposited on a polyvinylidene fluoride (PVDF) support layer was fabricated to improve membrane anti-fouling ability in seawater desalination without sacrificing permeability. The MXene-P (1H,1H,2H,2H-heptadecafluorodecyltrimethoxysilane-modified MXene) membrane exhibited optimal desalination performance, maintaining a water permeation flux of 1.88 kg m−2 h−1, and a salt rejection of nearly 100%. Its permeability was close to that of a pure PVDF porous membrane (1.95 kg m−2 h−1). A plausible explanation is that the porous MXene layer, enlarged interlayer spacing, and gaps created by the stacking of sheets provide multiple water transport channels, and the ultra-thin coating thickness minimizes the additional mass transfer resistance. Moreover, it was found that the performance of the MXene-P membrane remained stable within 120 h under actual seawater conditions, and no obvious contamination of the membrane surface was observed after this testing, which was attributed to the large water contact angle (150°) and high negative charge (−70 mV) of the coated layer. The maintenance of both long-term operational stability and high moisture permeability, with outstanding salt rejection, are essential for real seawater desalination driven by solar energy.