The honeycomb core sandwich structure has received wide attention in aeronautical and aerospace engineering in recent years, which is a structural composite material formed by adding an aluminum honeycomb core layer between two thin metal plates. The honeycomb core has high rigidity in the axial direction, but low rigidity in the radial direction, so many machining defects may easily take place under the action of the horizontal cutting force. To investigate how such defects affect the mechanical properties of aluminum honeycomb core sandwich structure, the mechanical response of honeycomb cores in a flat compression and the deformation process in a low-velocity impact were studied. By milling the aluminum honeycomb cores, the typical defects such as honeycomb wall tearing, folding, crushing, cracking, and debonding were obtained. In addition, a finite element model of the honeycomb sandwich structure with machining defects was created to simulate the flat compression and the low-velocity impact. Then the effects of machining defects on the impact properties under different impact conditions were compared and analyzed. The results show that the tearing has the greatest influence on the flat compression of the aluminum honeycomb core, the length and number of the tearing defect together affect the load carrying capacity of the sandwich structure, however the influences of the crushing and folding, cracking and debonding of the honeycomb wall are small. When the tearing length was 0.3L (L is the length of the honeycomb core wall) and tearing defect ratio was maintained below 8%, the ultimate load applied on the honeycomb sandwich structure and the energy absorption were less affected by the impact energy. The panel thickness has a great influence on the impact performance of the honeycomb sandwich structure, the greater panel thickness of the sandwich structure of the aluminum honeycomb core provides a greater ultimate load capability and a smaller influence of the machining defects on the impact performance of the sandwich structure, with a comprehensive consideration of both lightweight design and reducing the influence of the number of defects on the impact performance of the sandwich structure, the best choice of the skin panel thickness for the honeycomb core was 1 mm.