The work aims to study the plateau stress variation of honeycomb paperboard and fatigue damage mechanism under different conditions. First, honeycomb paperboard was subject to temperature and humidity pretreatment. Then, 5 precompression and different times of fatigue compression were carried out, followed by the quasi-static compression. Finally, the constitutive relation curves of honeycomb paperboard were obtained under different fatigue damage conditions. The fatigue damage of the honeycomb paperboard was caused by the reduction of the irregularly arranged stiffness of the paper fibers. Fatigue damage had great influence on the plateau stress of honeycomb paperboard. Under different fatigue damage conditions, fatigue damage had certain laws regarding the plateau stress of honeycomb paperboard. After the fatigue damage of honeycomb paperboard during transportation, the change of its plateau stress must be considered.