Background Past studies in the teaching context provided evidence of the role of mindfulness-based intervention in improving occupational wellbeing. This study aims to increase the extant knowledge by testing the mechanism that links teachers’ mindfulness at work to occupational wellbeing. Rooted in the job demand–resource model, the mindfulness trait is conceptualized as a personal resource that has the ability to impact and interact with job demands and resources, specifically workload stress appraisal and perceived meaningfulness of work, in affecting teachers’ burnout. Methods A sample of primary, middle, and secondary school teachers (N = 605) completed a questionnaire that aimed to assess teachers’ mindfulness trait and the measures of the quality of occupational life in the school context. Confirmatory factor analysis (CFA) was conducted to test the model fit indices; further analyses were performed to test the hypotheses about mediation and moderation effects. Results The CFA showed good model fit indices. Further analyses highlighted that teachers’ mindfulness is negatively associated with workload stress appraisal and that positively influenced work meaning, in turn mediating the relationship between mindfulness and burnout. Finally, mindfulness moderated the effect of workload stress appraisal on burnout. Conclusions Rooted in the job demand–resource model, this study emphasizes an underrepresented personal resource, that is, the mindfulness trait at work, and the links that favor its impact on burnout. Practical and future research implications are also discussed.