The optimal design of multilayer substrates containing the cutout under compression is very important to achieve maximum buckling resistance in comparison with structural weight, especially in aerospace structures. In this study, buckling and post-buckling behavior of composite laminated plates with orthogonal and symmetrical layup containing the cutout with different diameters has been investigated experimentally, semi-analytically, and numerically. To study the buckling of the composite plate with cutout semi-analytically, a finite strip method is developed. A finite element method was used for numerical analysis. The required material parameters for modeling were obtained from standard tests. The results of the current study show that the size of diameter of cutout does not have considerable effect on elastic rigidity of plate, but the buckling load significantly decreases by increasing cutout diameter. Also, buckling load and elastic rigidity of plate are considerably increased by increasing the number of composite layers. The thickness of plate has more effect on buckling load than the diameter of hole. Studies show that there is a good match between the results of buckling behavior derived from semi-analytical and finite element methods with experimental results.