Abstract Conventional cellulose-based nanocomposites production requires two separate unit operations for the processing: (i) cellulose nanofibrillation unit, and (ii) polymer nanocomposites compounding unit. This two-unit process could be less efficient in terms of energy usage and material handling compared to a one-unit process. Moreover, the present of downtime in between the two steps may affect the overall productivity of the product. In this study, a one-pot process was adapted for nanofibrillation of oil palm mesocarp fiber (OPMF) cellulose and subsequently compounding of the cellulose nanofiber (CNF) with polyethylene (PE) for composites making. Both of these steps were conducted in an extruder with specially-designed twin screw, to allow nanofibrillation and compounding to occur in the same unit. It was interesting to note that CNF produced had diameter range of 80–100 nm, with an aspect ratio of 260. These superior physical properties have led to the excellent mechanical properties of the PE/OPMF-CNF nanocomposites, whereby PE/OPMF-CNF (3 wt%) recorded an increment of 57 and 198% for tensile strength and flexural strength, respectively, compared to the neat PE. Homogeneous dispersion of CNF in the PE matrix was also observed, suggesting the suitability of the one-pot processing method for cellulose-based nanocomposites production. Overall performance of the nanocomposites was similar to that prepared in a two-pot process; with the one-pot process was almost doubled in the productivity compared to two-pot process. A two-step in one unit operation (2-in-1) would be an ideal process for nanocomposites making as this method may improve productivity, reduce downtime in between the two steps, could contribute to a lower capital and processing costs, and may have lower energy consumption. The one-pot process meets most of the green chemistry principles; suggesting the method as a sustainable and greener method for polymer nanocomposites production.