This study reports the combination of mechanochemistry and natural deep eutectic solvents (NADES) to produce nanocellulose with a one-step process, combining the advantages of both techniques. Two acidic NADES were chosen as solvents, both involving choline chloride as the hydrogen-bond acceptor (HBA); however, the hydrogen-bond donor (HBD) was oxalic acid dihydrate or citric acid monohydrate. NADES are successfully prepared by grinding the two products for 15 s. Then, cotton fibers were subjected to intense mechanical treatment for 1.5 h at room temperature, thus producing superficially carboxylated nanocellulose. In fact, shearing and impact forces provided by the milling promote the amorphous cellulose hydrolysis and the surface esterification of nanocellulose. Cellulose nanocrystals (CNCs) were then extracted with a yield of 65%, and their lengths were established at about 143 nm. Moreover, carboxylated CNCs showed a high thermal stability with an onset temperature of degradation of about 338 °C and a high crystallinity index of 93%.