In this study, the detonation diffraction and re-initiation processes around a single cuboid were studied experimentally. Experiments were performed in a 6-m-long duct with a cross section of 112 mm × 112 mm filled with stoichiometric methane–oxygen mixtures at initial pressures between 10 and 30 kPa. A cuboid was placed in the duct to form two perpendicular passages between the cuboid and the walls. Soot foils fixed on the side wall and bottom wall were used to characterize the cellular structure evolution process, from which the diffraction and re-initiation behavior of a detonation could be analyzed. The effects of the spacing between the cuboid and the top wall ( δ ) and the spacing between the cuboid and the side wall ( σ ) on diffraction and re-initiation were investigated systematically. It is shown that the diffraction and re-initiation of a detonation were influenced significantly by introducing a perpendicular channel. Compared with the unidirectional scenario, the boundary between the diffraction wave and the re-initiation region was not so sharp. Depending on the channel scale and mixtures sensitivity (or cell size, λ ), two re-initiation modes could be observed. For more sensitive mixtures ( δ / λ > 2 or σ / λ > 2 ), an overdriven detonation occurs first. The overdriven detonation propagates toward the edge, generating a secondary overdriven detonation near the wall through detonation reflection. The new one propagates forward and decays to a steady-state detonation. On the other hand, only one overdriven detonation occurs for less sensitive mixtures. For a given channel width, it was demonstrated that the diffraction area could be narrowed as the perpendicular channel width was increased. The inverse feedback mechanism between the two perpendicular diffraction waves was analyzed.