A study to produce cellulose nanofibrils (CNF) from Kraft cellulose pulp, an optimal enzyme mixture, was defined using a centroid simplex mixture design. The enzyme blend contains 69% endoglucanase and 31% exoglucanase. The central composite rotational design (CCRD) optimized the CNF production process by achieving a higher crystallinity index. It thus corresponded to a solid loading of 15 g/L and an enzyme loading of 0.974. Using the Segal formula, the crystallinity index (CrI) of CNF was determined by X-ray diffraction to be 80.87%. The average diameter of nanocellulose fibers measured by scanning electron microscopy between 550 - 600 nm for the CNF prepared by enzymatic hydrolysis and between 250 - 300 nm for the CNF produced by enzymatic hydrolysis with the optimal enzyme mixture followed by ultrasonic dispersion. Finally, synergistic interactions between the enzymes involved in nanocellulose production were demonstrated, with Colby factor values greater than one.