Hydrate adhesion is a challenging issue in some practical applications. However, most current anti-hydrate coatings fail to maintain their properties when subject to crude oil and corrosive contaminants. In addition, the effect of surface properties on the nucleation of hydrates is still unexplored from a microscopic perspective. In this study, a multifunctional amphiphobic PF/ZSM-5 coating consisting of 1H, 1H, 2H, 2H-perfluorooctyltriethoxysilane modified ZSM-5 zeolite (F/ZSM-5) and adhesive polyethersulfone was fabricated by the spraying method. The interfacial nucleation and adhesion of hydrates on substrates were studied from a microscopic perspective. The coating exhibited excellent repellencies to various liquids, including water, edible oil, liquid paraffin, vacuum pump oil, n-hexadecane, and crude oil. The tetrabutylammonium bromide (TBAB) hydrate is readily nucleated on the bare Cu surface. In contrast, the coated substrate effectively inhibited the hydrate nucleation on the surface and even reduced the adhesion force to 0 mN/m. Furthermore, this coating was fouling- and corrosion-resistant and can maintain an ultralow hydrate adhesion force even after immersion in crude oil or TBAB solution for 20 and 300 d, respectively. The durable anti-hydrate performance of the coating was attributed mainly to the unique architecture and excellent amphiphobic properties enabling stable air cushions between the solid-liquid interface.