A strong photoluminescence (PL) enhancement of monolayer MoS₂ is achieved through defect engineering and oxygen bonding. Micro-PL and Raman images show that PL enhancement occurs at cracks/defects formed during high-temperature vacuum annealing. The PL enhancement at these sites can be as high as thousands of times after considering the laser spot size. The main reasons for this enhancement include oxygen chemical adsorption-induced heavy p-doping and the conversion from trion to exciton, as well as the suppression of non-radiative recombination of excitons at defect sites, verified by low-temperature PL measurements. First-principles calculations reveal a strong binding energy of ~2.395 eV for oxygen molecule adsorbed on an S vacancy of MoS₂. Chemical adsorbed oxygen provides a much more effective charge transfer (0.997 electrons per O₂) compared to physical adsorbed oxygen on ideal MoS₂ surface. Defect engineering and oxygen bonding can be easily realized by oxygen plasma irradiation. X-ray photoelectron spectroscopy confirms the formation of Mo-O bonding. The results provide a new route for modulating the optical properties of two-dimensional semiconductors. The strong and stable PL from defect sites of MoS₂ may have promising applications in optoelectronic devices. Keywords: MoS₂, photoluminescence, defect engineering, plasma, oxygen bonding, excitons.A strong photoluminescence (PL) enhancement of monolayer MoS₂ is achieved through defect engineering and oxygen bonding. Micro-PL and Raman images show that PL enhancement occurs at cracks/defects formed during high-temperature vacuum annealing. The PL enhancement at these sites can be as high as thousands of times after considering the laser spot size. The main reasons for this enhancement include oxygen chemical adsorption-induced heavy p-doping and the conversion from trion to exciton, as well as the suppression of non-radiative recombination of excitons at defect sites, verified by low-temperature PL measurements. First-principles calculations reveal a strong binding energy of ~2.395 eV for oxygen molecule adsorbed on an S vacancy of MoS₂. Chemical adsorbed oxygen provides a much more effective charge transfer (0.997 electrons per O₂) compared to physical adsorbed oxygen on ideal MoS₂ surface. Defect engineering and oxygen bonding can be easily realized by oxygen plasma irradiation. X-ray photoelectron spectroscopy confirms the formation of Mo-O bonding. The results provide a new route for modulating the optical properties of two-dimensional semiconductors. The strong and stable PL from defect sites of MoS₂ may have promising applications in optoelectronic devices. Keywords: MoS₂, photoluminescence, defect engineering, plasma, oxygen bonding, excitons.