Fatigue crack growths of foam core sandwich structure loaded in three-point bending under room temperature, low temperature and hygrothermal environment have been investigated. The fatigue life and S-N curve are given, and the results of flexural fatigue test confirm the obvious effect of low temperature and hygrothermal environment on the fatigue life of foam core sandwich structure. Core shear was found to be the dominant failure mode under fatigue loading condition at all of three environments. Three-dimensional numerical simulation of the progressive collapse of foam core sandwich structure was conducted using user subroutine USDFLD in FEM software ABAQUS. The maximum stress failure criterion and Hashin failure criterion were used to judge the failure of foam core and skin, respectively. Finite element analysis explains the crack initiation and propagation under flexural load, and progressive damage method can be used to simulate the failure of foam core sandwich structure.