In the present work, the surface behavior of cotton fabrics coated with a series of bio-based polybenzoxazines is explored. Herein, we report the design and synthesis of bio-based benzoxazine monomers (C-x) using cardanol (C) and seven different amines (x = ba, ha, dda, oda, ddm, jef, and fa). The molecular structures of the benzoxazine monomers have been confirmed using FTIR and NMR analyses. The microstructure of the polybenzoxazine-coated cotton fabrics observed from FE-SEM reveals that formation of rough nanostructure is influenced by molecular structure of monomers. Further, surface analysis shows that poly(C-dda)-coated cotton fabric offers superior water contact angle (WCA = 155° ± 3) with low sliding angle (6°). Also, poly(C-dda)-coated cotton fabric delivers the lowest surface energy (14.1 mN/m) and high resistance against acidic and alkaline media. Subsequently, oil–water separation investigation shows that the poly(C-dda)-coated cotton fabric yields 99% of separation efficiency with flux value of 7200 L/m2h. Thus, the cardanol-based polybenzoxazine-coated cotton fabrics prepared in the present work can find application in the field of oil–water separation due to their superior water-repellent nature.