Traditionally, obtaining 2D materials involves the stripping of layered crystals. However, the anisotropic bonding arrangement within the 3D crystals shows that they are mechanically similar to 2D crystals and can also be stripped into nanosheets. This report describes the process of preparing 2D nanosheets from six representative 3D metal-organic skeletons (MOFs) by liquid phase stripping. Notably, the cleavage plane of the stripped nanosheets is perpendicular to the direction of the minimum elastic modulus (Emin) within the original 3D skeleton. The results show that the resultant in-plane and out-of-plane bonding forces of the stripped nanosheets are related to the maximum elastic modulus (Emax) and Emin of the 3D skeleton, respectively. Emax affects the ease of cleavage of adjacent layers, while Emin determines the ability to resist layer cracking. Therefore, the combination of a larger Emax and a smaller Emin indicates that the stripping process works, and vice versa. The ratio of Emax/Emin (expressed as Amax/min) is used as a general indicator to quantify the ease of mechanical stripping of 3D MOF. This ratio can be easily obtained through mechanical experiments and calculations, and can be a valuable indicator for selecting a suitable stripping method to produce surfactant free 2D nanosheets from a variety of 3D materials.