Two-dimensional (2D) materials tend to have the preferable formation of vacancies at the outer surface. Here, contrary to the normal notion, we reveal a type of vacancy that thermodynamically initiates from the interior part of the 2D backbone of germanium selenide (γ-GeSe). Interestingly, the Ge-vacancy (V) in the interior part of γ-GeSe possesses the lowest formation energy amongst the various types of defects considered. We also find a low diffusion barrier (1.04 eV) of V, which is half of those of sulfur vacancies in MoS. The facile formation of mobile V is rooted in the antibonding coupling of the lone-pair Ge 4s and Se 4p states near the valence band maximum, which also exists in other gamma-phase MX (M = Sn, Ge; X = S, Te). The V is accompanied by a shallow acceptor level in the band gap and induces strong infrared light absorption and p-type conductivity. The V located in the middle cationic Ge sublattice is well protected by the surface Se layers - a feature that is absent in other atomically thin materials. Our work suggests that the unique well-buried inner V, with the potential of forming structurally protected ultrathin conducting filaments, may render the GeSe layer an ideal platform for quantum emitting, memristive, and neuromorphic applications.