This study reports a significant enhancement of photoluminescence (PL) in monolayer MoS₂ through defect engineering and oxygen bonding. Micro-PL and Raman images reveal that the PL enhancement occurs at cracks/defects formed during high-temperature vacuum annealing, with enhancements up to thousands of times compared to the laser spot size. The main reasons for this enhancement include: (1) oxygen chemical adsorption-induced heavy p-doping and conversion from trions to excitons, and (2) suppression of non-radiative recombination of excitons at defect sites, verified by low-temperature PL measurements. First-principles calculations show a strong binding energy of ~2.395 eV for oxygen molecules adsorbed on S vacancies in MoS₂. Chemical adsorbed oxygen provides more effective charge transfer (0.997 electrons per O₂) compared to physical adsorbed oxygen. The defect engineering and oxygen bonding can be achieved through oxygen plasma irradiation, and X-ray photoelectron spectroscopy confirms the formation of Mo-O bonds. These findings provide a new route for modulating the optical properties of two-dimensional semiconductors, with potential applications in optoelectronic devices.This study reports a significant enhancement of photoluminescence (PL) in monolayer MoS₂ through defect engineering and oxygen bonding. Micro-PL and Raman images reveal that the PL enhancement occurs at cracks/defects formed during high-temperature vacuum annealing, with enhancements up to thousands of times compared to the laser spot size. The main reasons for this enhancement include: (1) oxygen chemical adsorption-induced heavy p-doping and conversion from trions to excitons, and (2) suppression of non-radiative recombination of excitons at defect sites, verified by low-temperature PL measurements. First-principles calculations show a strong binding energy of ~2.395 eV for oxygen molecules adsorbed on S vacancies in MoS₂. Chemical adsorbed oxygen provides more effective charge transfer (0.997 electrons per O₂) compared to physical adsorbed oxygen. The defect engineering and oxygen bonding can be achieved through oxygen plasma irradiation, and X-ray photoelectron spectroscopy confirms the formation of Mo-O bonds. These findings provide a new route for modulating the optical properties of two-dimensional semiconductors, with potential applications in optoelectronic devices.