Polyethylene (PE) is one of the most highly consumed petroleum-based polymers and its accumulation as waste causes environmental pollution. In this sense, the use of microorganisms and their enzymes represents the most ecofriendly and effective decontamination approach. In this work, molecular docking simulation for catalytic enzyme degradation of PE was carried out using individual enzymes: laccase (Lac), manganese peroxidase (MnP), lignin peroxidase (LiP) and unspecific peroxygenase (UnP). PE-binding energy, PE-binding affinity and dimensions of PE-binding sites in the enzyme cavity were calculated in each case. Four hypothetical PE biodegradation pathways were proposed using individual enzymes, and one pathway was proposed using a synergic enzyme combination. These results show that in nature, enzymes act in a synergic manner, using their specific features to undertake an extraordinarily effective sequential catalytic process for organopollutants degradation. In this process, Lac (oxidase) is crucial to provide hydrogen peroxide to the medium to ensure pollutant breakdown. UnP is a versatile enzyme that offers a promising practical application for the degradation of PE and other pollutants due to its cavity features. This is the first in silico report of PE enzymatic degradation, showing the mode of interaction of PE with enzymes as well as the degradation mechanism.