In this study, we developed a facile, efficient, and eco-friendly strategy for fabricating hydrophobic cotton fabrics using poly(glycidyl methacrylate) (PGMA) nanoparticles (NPs), which were synthesized via a radical-induced dispersion polymerization technique. Interestingly, the long alkyl chain of octadecyl mercaptan provides a low surface free energy, while PGMA NPs act as anchors, forming covalent bonds with the surface of the cotton fabric, resulting in greater roughness. The covalent bonds, formed via the epoxy ring-opening reaction between the glycidyl groups of the PGMA NPs, react with the hydroxyl groups on the surface of the cotton fabric. The chemical structure, morphology, and mechanical properties of the fabric were characterized using solid-state nuclear magnetic resonance spectroscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, scanning/transmission electron microscopy, energy-dispersive spectroscopy, Brunauer-Emmett-Teller analysis, X-ray photoelectron spectroscopy, and thermogravimetric analysis. Mechanical characterizations suggested that the tear strength decreased for the modified fabric, whereas the stiffness was double that of neat cotton. The modified cotton fabric exhibited nano- and microscale roughness, which resulted in increased hydrophobicity, with a contact angle of 130°. The modified cotton exhibited self-cleaning properties and various droplet resistance properties, and thus has promising applications in different fields.