The work aims to study the fatigue damage of cushion packaging of stacked products after vibration and shock under continuous complex transportation conditions. Miner’s rule, Dirlik's method and Steinberg’s three-interval method, combined with Workbench and ncode fatigue analysis module, were used to build a two-layer stacked packaging model for finite element simulation. The vibration fatigue damage of cushion packaging under complex continuous working conditions was simulated by vibration excitation under different working conditions and the corresponding fatigue result and fatigue life cloud diagram were obtained. Under complex working conditions, the fatigue life of corrugated packaging was 9.26×109 and the damage value at the maximum node was 1.08×10−10. The fatigue life of EVA internal cushion liner was 1.882×1014 and the damage value at the maximum node was 5.313×10−15. The vulnerable points of stacked packaging model were mainly concentrated at the corners and edges of internal and external cushion packaging. Dirlik and Steinberg methods were used to prove that the residual life of the cushion was 2.6×104 h and 9.198×105 h under the complex transportation condition for 16 h. The Miner’s rule was used to prove that the cushion packaging structure could play a good role in protecting the internal products. By this method, the fatigue life of stacked packaging can be analyzed reliably under complex working conditions, and some suggestions and reference ideas are provided for the selection of working conditions and the optimal design of structure of stacked packaging products during transportation under multiple working conditions.