Recently, monolayer MoS₂ has attracted the huge attention of the research community due to its inherent fascinating electronic and optoelectronic properties for various applications such as sensor, catalysis, and flexible electronics [1,2]. The structural stability of CVD-grown monolayer MoS₂ is of great importance for nano and optoelectronic-based applications. Understanding the long-term ambient exposure effect on monolayer MoS₂ is important for acquiring many overreaching goals of this material. Here, in this work, we have reported the systematic study of monolayer MoS₂ degradation under long-term exposure in ambient conditions and in high vacuum environment. Uniform and highly crystalline monolayer MoS₂ deposited on 300 nm SiO₂/Si substrate via atmospheric pressure chemical vapor deposition system. It is observed that moisture penetrates between MoS₂ and substrate surface due to the opposite surface energy nature of MoS₂ and SiO₂/Si which oxidizes the deposited MoS₂ layer and peel off the MoS₂ layer day by day from the substrate surface. Interestingly, it is observed that MoS₂ degradation started from edges to the nucleus and the degradation rate of monolayer MoS₂ in a high vacuum environment is very less as compared to ambient exposure. This suggests that oxygen concentration is one of the important parameters in the structural degradation of monolayer MoS₂. Therefore, to preserve the long-term structural and chemical stability of monolayer MoS_2, it is necessary to isolate it from oxygen and moisture environment.