This research is devoted to studying the capability of the damage-entropy model for fatigue life prediction of the off-axis unidirectional composites. The damage process in composites was characterized by the micro-continuum damage mechanics (MCDM) and an available reformulated form of the Mori-Tanaka model was used. In the present study, the fracture fatigue entropy (FFE), which is the accumulated entropy generation up to final failure during the fatigue process, was considered as a fatigue failure criterion for the off-axis unidirectional composites. One of the outstanding characteristics of the damage-entropy model is considering the self-heating and temperature evolution during the fatigue life that is due to the damage evolution, irreversible work, and internal friction in composites. Moreover, the dissipated heat due to the viscoelastic intrinsic property of the polymeric matrix was considered. The proposed model was validated by investigating the fatigue behavior of unidirectional T800H/2500 and E-glass/epoxy composites under tension-tension cyclic loading. Results show that the fatigue life prediction of the damage-entropy model is in good agreement with the experimental data.