In this article, the description of a novel damage-coupled constitutive formulation for the mechanical behavior of semicrystalline polyethylene is presented. The model attempts to describe the deformation and degradation processes in polyethylene considering the interplay between the amorphous and crystalline phases and following a continuum damage mechanics approach from a microstructural viewpoint. For the amorphous phase, the model is developed within a thermodynamic framework able to describe the features of the material behavior. Amorphous phase hardening is considered into the model and associated with the molecular configurations arising during the deformation process. The equation governing damage evolution is obtained by choosing a particular form based on internal energy and entropy. For the crystalline phase, the proposed model considers the deformation mechanisms by the theory of crystallographic slip and incorporates the effects of intracrystalline debonding and fragmentation. The model generated within this framework is used to simulate uniaxial tension and simple shear of high density polyethylene. The predicted stress-strain behavior and texture evolution are compared with experimental results and numerical simulations obtained from the literature. By incorporating a damage mechanics approach, the proposed model predicts the progressive loss of material stiffness attributed to the crystal fragmentation and molecular debonding of the crystal-amorphous interfaces.