This work reports molecular beam epitaxy (MBE) of two-dimensional (2D) GaSe on a three-dimensional (3D) GaN/sapphire platform, which is widely recognized as a potential candidate for electronics and optoelectronic applications. Herein, we have demonstrated that regulating the adatoms’ mobility via growth temperature can enable a growth mode transition from screw dislocation-driven (SDD) to layer-by-layer (LBL) in the epitaxy of 2D-GaSe. Typically, the high-density and uniform spiral structure is observed in the SDD-GaSe at low temperatures (≤500 °C), while μm-scale triangular LBL-GaSe morphology was dominant at high[1]temperature regime. The diverse optical properties of 2D-GaSe layers under different growth modes were comprehensively investigated, where the unique behaviors of the in-plane propagation (E1g) Raman mode in the SDD-GaSe as well as the resonant effect in the LBL-GaSe have been reported for the first time. Moreover, a significant blueshift of ∼0.21 eV in PL spectra of the LBL[1]GaSe layer with respect to the SDD-GaSe layer is indicated. This opens up the probability for band structure engineering of the 2D[1]GaSe epitaxial layers by switching the growth mode. Attractively, the LBL-GaSe multilayers exhibited a current density ∼120 nA/ cm2 at zero bias; thus, it could be an auspicious candidate for self-powered photodetecting applications.