In this article, we present a fab-compatible metal–organic chemical vapor deposition growth process, realized in a hydrogen ambience, of two-dimensional (2D) layered GaSe on 200 mm diameter Si(111) wafers. Atomic scale characterization reveals initial stages of growth consisting of passivation of the H–Si (111) surface by a half-monolayer of GaSe, followed by nucleation of 2D-GaSe from the screw dislocations located at the step edges of the substrate. We, thus, demonstrate that by using a Si wafer that is slightly misoriented toward [1̄1̄2], the crystallographic orientation of 2D-GaSe can be step-edge-guided. It results in a coalesced layer that is nearly free from antiphase boundaries. In addition, we propose a sequential process to reduce the density of screw dislocations. This process consists in a subsequent regrowth after partial sublimation of the initially grown GaSe film. The local band bending in GaSe near the antiphase boundaries measured by Kelvin probe force microscopy emphasizes the electrical activity of these defects and the usefulness of having a nearly single-orientation film. Such a low defectivity layer opens up the way toward large-scale integration of 2D-optical transceivers in Si CMOS technology.