Oil–water separation is among the critical issues worldwide due to recent massive oil spills. Moreover, domestic and industrial water pollution due to oil discharge affects marine and aquatic life. Cotton is the most predominant fiber globally because of its use as a principal and popular clothing material. Cotton is also the leading raw material for technical and functional textile applications. In this study, the fabric was cured with poly (methyl methacrylate) (PMMA) nanoparticles to develop hydrophobic and oleophilic cotton fabrics. The dehydrating agents, N,N′-dicyclohexylcarbodiimide (DCC) and dimethyl aminopyridine (DMAP), were used to catalyze the esterification. The results proved that the excellent hydrophobicity of modified cotton fabric provides a water contact angle higher than 140°. In addition, Fourier transforms infrared (FTIR) spectroscopy, as well as X-ray photoelectron spectroscopy (XPS) analysis, confirmed the fabric surface modification. Surface morphological analysis by scanning electron microscope (SEM) revealed the uniform rough surface structure of the modified fabric with nano-coating. The modified fabric resulted in the high separation efficiency of oil and water, suggesting this strategy to be suitable for advanced oil–water separation.