We report an anomalous phase transition in compressed In2Se 3. The high-pressure studies indicate that In2Se 3 transforms to a new isosymmetric R-3m structure at 0.8 GPa whilst the volume collapses by ∼7%. This phase transition involves a pressure-induced interlayer shear glide with respect to one another. Consequently, the outer Se atoms of one sheet locate into the interstitial sites of three Se atoms in the neighboring sheets that are weakly connected by van der Waals interaction. Interestingly, this interlayer shear glide changes the stacking sequence significantly but leaves crystal symmetry unaffected. This study provides an insight to the mechanisms of the intriguing isosymmetric phase transition.