First-principles calculations based on density functional theory are employed to investigate the impact of vacancy defects on the optoelectronic properties of Bi4O5Br2. The results indicate that vacancy defects induce minimal lattice distortion in Bi4O5Br2 without compromising its structural stability. Oxygen or bromine vacancies are more likely to occur than bismuth vacancies. The introduction of a bismuth vacancy leads to n-type semiconductor behavior in the Bi4O5Br2 system, while the creation of an oxygen vacancy reduces the bandgap and enhances the light absorption capacity. Bi4O5Br2 with three coordinated oxygen vacancies exhibits a higher effective electron–hole pair mass ratio, which is advantageous for the efficient separation of electron–hole pairs. Bi4O5Br2 with three coordinated oxygen vacancies exhibits enhanced absorption and reflection coefficients in the visible-light region compared to other systems, indicating that oxygen vacancy defects significantly promote visible-light absorption and electron–hole separation. This research provides new theoretical insights for understanding and optimizing the performance of photocatalysts based on Bi4O5Br2.