In this contribution, alkaline carbonates were used as catalyst to develop an one-pot approach for esterification between cellulose and methacrylate anhydrides in aqueous solution. FTIR, 13C CP/MAS NMR and XRD analysis revealed successful esterification in amorphous domains of cellulose without affecting the cellulose crystal structure. The obtained methacrylated cellulose was amenable to further functionalization via thiol–ene click reactions. After this esterification under alkaline aqueous condition, cellulose can be easily grafted with thiolated motifs including fluorophores and bioactive peptide. Our work demonstrates an easy strategy for cellulose modification and functionalization and will greatly promote the wide-spread applications of cellulose-based materials.