Global social awareness of bioproducts has motivated the current work on sustainable nanocellulose modifications for diverse packaging applications. Agro-derived cellulose nanofibrils (CNFs) were mildly acetylated in an aqueous system with acetic acid and acetic anhydride for biobased coatings applied by vacuum-assisted methods, followed by thermal drying, which was found to improve oleophobic and hydrophobic properties. The compositional and morphological aspects were confirmed by time-of-flight secondary ion mass spectrometry (TOF-SIMS), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and optical profilometry. The barrier and mechanical performances of the prepared substrates were evaluated using oil and grease resistance kits and hot oil tests, air permeability, water contact angle (WCA), and tensile and fold tests. All coated papers passed with the highest kit 12, showing only 0–1.04% hot oil absorption and zero Gurley air permeability. The coated paper exhibited the highest WCA of ∼86° and the lowest surface energy of 31.70 mN/m. Furthermore, the coated paper exhibited an excellent dry tensile index of 71.06–75.34 N·m/g, which could be sustained even under wet conditions with a 21.79% increase of wet tensile strength over the base paper and improved mechanical flexibility of up to 400 double folds. Therefore, the prepared substrates can be effective biobased alternatives for flexible packaging and other applications.