Abstract Monolayer (ML) molybdenum disulfide (MoS₂) is a novel 2-dimensional (2D) semiconductor whose properties have many applications in devices. Despite its potential, ML MoS₂ is limited in its use due to its degradation under exposure to ambient air. Therefore, studies of possible degradation prevention methods are important. It is well established that air humidity plays a major role in the degradation. In this paper, we investigate the effects of substrate hydrophobicity on the degradation of chemical vapor deposition (CVD) grown ML MoS2. We use optical microscopy, atomic force microscopy (AFM), and Raman mapping to investigate the degradation of ML MoS2 grown on SiO2 and Si3N4 that are hydrophilic and hydrophobic substrates, respectively. Our results show that the degradation of ML MoS₂ on Si3N4 is significantly less than the degradation on SiO2. These results show that using hydrophobic substrates to grow 2D transition metal dichalcogenide ML materials may diminish ambient degradation and enable improved protocols for device manufacturing.