The effect of anisotropy on high‐cycle fatigue (HCF) property along the rolling direction (RD) and the transverse direction (TD) of a 7××× aluminum alloy super thick plate is mainly investigated in this study. The results show a similar microstructure at different thicknesses, and the HCF properties are close as well. The fatigue fracture morphologies show that the fatigue crack sources are all located on the surfaces of the RD and TD specimens. By considering the differences in the HCF properties, there is only a slight anisotropy effect at the center thickness of the plate, which can be attributed to the tensile anisotropy caused by textures. Besides, the fatigue damage degree along the TD is slightly higher than that along the RD at the center thickness. The reason can be explained by two aspects: one is the higher probability of defect occurrence along the TD compared with that along the RD which is analyzed by the previously proposed Yield strength‐Tensile strength‐Fatigue strength model, and the other is the influence of the textures. The combination of hard and soft orientations may cause fatigue damage localization easily in the soft‐oriented grains which accelerates the fatigue failure.