We report the first demonstration of beta-phase gallium oxide (β-Ga2O3) as optical waveguides on sapphire substrates grown by metal-organic chemical vapor deposition (MOCVD). Their propagation losses in the visible spectrum were comprehensively studied via experiments and simulations of the finite difference method by varying the dimensions of the waveguides. The fabrication process of the waveguides was shown and their propagation losses were measured by collecting the top scattered optical power along the propagation direction using a charge-coupled device (CCD) camera. The minimum measured loss was 3.7 dB/mm at a wavelength of 800 nm depending on the dimensions of the waveguides. In addition, we compared the losses of waveguides with different widths, heights, wavelengths, and polarizations. It is revealed that the total propagation loss is mainly contributed by the bulk and sidewall scattering. Combined with theoretical simulations, various loss mechanisms from two-photon absorption, sidewall scattering, top surface scattering, and bulk scattering, were discussed for β-Ga2O3 waveguides, and their contributions to the total optical loss were estimated. After all these mechanism analyses on absorption and scattering, a large improvement and optimization were applied to the material quality and etching recipe, which improves the top surface and sidewall roughness respectively. This work provides valuable information for the fabrication of optical devices based on Ga2O3 material, which is promising for applications in on-chip high-speed interconnections and UV–NIR nonlinear optics.