High cycle fatigue properties of 2124 aluminum alloy plates with different thickness were investigated by determining fatigue S−N curves, fatigue crack growth rates and fracture toughness of 2124‐T851 aluminum alloy plates with the thickness of 30 mm, 40 mm and 55 mm, respectively. Fatigue fracture behaviors of alloy plates were also analyzed and discussed using scanning electron microscope morphology observation, energy spectrum analysis, X‐ray diffraction phase analysis and transmission electron microscopy observation in this paper. The results indicate that plate thickness affects the comprehensive fatigue properties of 2124 aluminum alloy plates. Thinner plate achieves better comprehensive fatigue properties. Due to the different amount of deformation during hot rolling, the variation of microstructure of alloy plates with different thickness mainly concentrates on the difference of grain sizes, substructure and volume fraction of grain boundaries. The thinner the plate, the smaller the grain sizes and therefore the thinner plate produces a higher volume fraction of grain boundaries and substructure, and a greater resistance to fatigue crack growth, thus thinner plate exhibits better fatigue properties.