7065 aluminum alloy thick plate with thickness of 125 mm was fabricated by semi-continuous casting→homogenization→hot rolling→solid solution→aging treatment. The microstructure evolution at different wall thickness positions of 7065 aluminum alloy thick plate and the mechanical properties of the aged alloy were studied by means of metallographic microscope, scanning electron microscope, transmission electron microscope, differential scanning calorimeter, X-ray diffractometer and universal stretching machine. The experimental results show that the as-cast microstructure of 7065 aluminum alloy thick plate is finer in the surface layer and coarser in the central layer, the volume fraction of η phase in the homogenized state is 64.5% lower than that in the as-cast state, and the deformation degree of the hot-rolled surface layer is the highest, while the deformation degree of the central layer is the smallest. In the aged microstructure, the precipitated phase is mainly the nano-scale η' phase precipitated in the grain, and the recrystallization degree and precipitated phase fraction of the surface layer are higher than that of the central layer. 7065 aluminum alloy thick plate has little difference in mechanical  roperties at different positions. Along the rolling direction (RD), the strength of the central layer is the highest, and the tensile strength, yield strength and elongation are 560.1 MPa, 539.6 MPa and 13.7%, respectively. Along the transverse direction (TD), the strength of the 1/4 layer is the highest, and the tensile strength, yield strength and elongation are 563.1 MPa, 541.3 MPa and 12.2%, respectively. This study provides a basis for the designing and fabricating 7xxx aluminum alloy thick plates with excellent comprehensive mechanical properties and homogeneity.