The production of large quantities of 2D materials in solution with well-controlled morphological properties of the nanosheets is not only a technological challenge but also a fundamental one, because several scientific aspects still need to be clarified for a detailed understanding of the fragmentation mechanisms and the control of the final products. Furthermore, it is necessary to develop fast and reliable protocols to measure and analyze a large number of 2D objects and as well as to find a set of “robust” parameters to achieve an accurate multi-scale description of the system. Here we show how these problems can be fruitful solved by using a statistical approach. In particular, the study of the distribution of the morphological parameters represents the key-factor i) to understand the physical mechanisms of the fragmentation in liquid, ii) to test the theoretical models and iii) to explore the mechanical and the structural properties of both the starting material and the final fragments. 1 Recently, we developed a fast and automatic procedure based on topographic images to measure, one by one, the exact shape and size of thousands of nanosheets obtained by exfoliation and fragmentation in general. 2 Here we monitored the time evolution of the area and the shape distribution of 2D single sheets of graphene oxide (GO) in water during extended sonication treatment. Combining the analysis of images acquired with different microscopies, we monitored the 2D fragments from the millimeter to the nanometer scale. In particular, we showed that the quantitative analysis provides to measure the mechanical properties of the GO sheet such as the fracture …