The perpendicularity error of the holes is prone to occur in the process of manual hole making or robot hole making, which leaves a safety hazard for the composite structure. In this study, the fatigue tests are carried out on the Carbon Fibre-reinforced Polymer (CFRP) single-lap single-bolt joints and effects of the perpendicularity error on the fatigue behaviors are studied. By combining the permanent displacement and stiffness of the joints, the evolution of fatigue damage is analyzed. The results show that the perpendicularity error causes stress concentration and hole fastener clearance near the hole entrance under the preload. The perpendicularity error in the 0° direction will greatly reduce the high-cycle fatigue and the impact on the low-cycle fatigue is relatively small, while the error in the 180° direction is just the opposite. The fatigue life is negatively correlated with the angle of the perpendicularity error. The effect of perpendicularity error in 0° direction on the fatigue damage evolution is to speed up the accumulation of damage, while the effect of error in 180° direction is mainly to cause more damage in the early stage of cyclic loading. The effect of perpendicularity error on the stiffness during fatigue loading is relatively insignificant.