To accurately predict the curing deformation of sandwich structures with variable thickness layup, a numerical simulation of the curing process of AS4/8551 carbon fiber/epoxy resin composite-Nomex honeycomb sandwich structure was conducted based on the thermal-chemical-structural multiphysics coupling method. Considering the influence of material time-varying characteristics, a three dimensional finite element model of sandwich structure was established by combining the transient linear elastic constitutive model of composites, micromechanics theory, and an improved Gibson equivalent theory. The distribution relationship between the curing degree field, temperature field, and stress-strain field of the structure throughout the entire curing cycle was studied. The simulation results were compared and validated against existing experimental data. Finally, the influence of pre-curing process on the structural rebound deformation was analyzed through the analytical model. The results show that the established finite element model can accurately reflect the curing process of the structure, with average prediction error of 4.8% and a maximum prediction error of no more than 6.0% for curing deformation. The variable thickness layup design has a significant impact on the curing stress of the thinner panel, resulting in upward shear stress along the thickness direction. During the cooling stage, these stresses concentrate at the ends of the structure and transforms into structural warping. The pre-curing preocess of the panels weakens the influence of curing heat release and material anisotropy on the curing deformation of the sandwich structure. At a pre-curing degree of 0.25, the reduction in maximum curing deformation reaches 14.78%. The research results provide important references for improving the manufacturing accuracy and optimizing the processes of complex designed honeycomb sandwich parts.