Considering a variety of two‐dimensional (2D) materials, metal chalcogenide monolayers, including transition metal dichalcogenides, group‐IV and group‐III monochalcogenides, and copper sulfide, are outstanding in the field of microelectronics and optoelectronics. Devices constructed of these 2D materials could be sensitively affected by ambient gases, such as O2 molecules. Regarding this significant issue, here we review the oxidation behaviors of 2D metal chalcogenides, especially for perfect and defective monolayers. Perfect monolayer metal chalcogenides are resistant to oxidation, resulting from the large activation energies for chemisorption and dissociation of O2 molecules during the reaction process. However, the defective monolayers with vacancies are prone to be oxidized with small activation energies. Interestingly, oxygen atoms can fill into the chalcogen vacancy sites and further maintian the electronic band structures of the perfect systems – the band gaps and the carrier effective masses are only moderately modified by the oxygen atoms. These fundamental understandings help to improve the use of monolayer metal chalcogenides toward the development of novel 2D devices with high stability and excellent performance.