The aim of this paper is to study the mechanical behavior of corrugated board boxes, focusing attention on the strength that the boxes are able to offer in compression under stacking conditions. A preliminary design of the corrugated cardboard structures starting from the definition of each individual layer, namely the outer liners and the innermost flute, was carried out. For this purpose, three distinct types of corrugated board structures that include flutes with different characteristics, namely the high wave (C), the medium wave (B), and even the micro-wave (E), were comparatively evaluated. More specifically, the comparison is able to show the potential of the micro-wave which would eventually allow a significant saving of cellulose in the fabrication process of the boxes, thus reducing the manufacturing costs and causing a lower environmental footprint. First, experimental tests were carried out to determine the mechanical properties of the different layers of the corrugated board structures. Tensile tests were performed on samples extracted from the paper reels used as base material for the manufacturing of the liners and flutes. Instead, the edge crush test (ECT) and box compression test (BCT) were directly performed on the corrugated cardboard structures. Secondly, a parametric finite element (FE) model to allow, on a comparative basis, the study of the mechanical response of the three different types of corrugated cardboard structures was developed. Lastly, a comparison between the available experimental results and the outputs of the FE model was carried out, with the same model being also adapted to evaluate additional structures where the E micro-wave was usefully combined with the B or C wave in a double-wave configuration.