Nowadays, the issue of teachers' psychological well-being causes serious concern, especially in Malaysia. Many studies related to psychological well-being have focused on students rather than on the health and well-being of teachers. Thus, the current study investigated the determinants of psychological well-being (depression, anxiety and stress) from the psychosocial work environment (job control, job demands and social support), and examined the moderating role of job control and social support in the relationship between job demands and psychological well-being among teachers. The design of this study was quantitative research through a survey questionnaire. The sample consisted of 335 high school teachers (23.3%-male; 76.7%-female) who responded to measuring scales of job demands, job control, social support, depression, anxiety and stress, and socio-demographic profile. The data were analyzed using two statistical methods, namely descriptive and inferential statistics. The hierarchical linear regression model was used to analyze the data by assisting the statistical software, i.e., SPSS-23. The results showed that job demands, job control and social support significantly predicted teachers' psychological well-being. Furthermore, the effect of job demands on teachers' depression and anxiety was partially moderated by job control and social support. In conclusion, this study has successfully identified the significant predictors of teachers' psychological well-being and the role of job control and social support as a moderating variable to teachers' psychological well-being in Malaysia. The result provides insights and contributes to the literature of teachers' psychological well-being determinants and involves Malaysian respondents with a collectivistic eastern culture.