Laser shock peening (LSP) as an emerging surface peening technology that is widely used in aerospace manufacturing. The effect of laser shock peening on surface integrity and high cycle fatigue (HCF) and very high cycle fatigue (VHCF) properties of 2024-T351 aluminum alloy was investigated in this study. Accordingly, the surface roughness, surface topography, microstructural, microhardness and residual stress of specimens treated with two different LSP pulse energy levels (10 J and 20 J) were analyzed. Additionally, the HCF and VHCF test was performed by ultrasonic fatigue test system. The results showed that surface roughness Ra value and microhardness of LSP treated specimens increased by a maximum of 89.37% and 16.3% comparing to the untreated specimen, respectively. X-ray diffraction analysis also showed that subgrain sizes were refined to the nanoscale. Furthermore, high-level compressive residual stresses (the maximum value about −210 MPa with 700 μm thickness) were introduced to the surface layer of the specimens. The S-N curve results showed that LSP treatment reduced the fatigue life of specimens, and the higher the laser pulse energy, the more obvious the effect of reduction. The fatigue fracture of specimens was analyzed via scanning electron microscope and residual stress distribution map. It is observed that fatigue cracks are predominantly initiated at fractured secondary phase particle locations in a VHCF range for untreated specimens. However, for LSP specimens, surface and internal crack initiation mechanisms were both observed. Under low and intermediate stress levels, the tensile residual stresses (which coexists with the compressive residual stresses) initiated fatigue cracks from the interior of the specimens; under high-stress levels, fatigue cracks were initiated at the material surface.