<p>The mechanisms and boundary conditions underlying the influence of humble leadership on teacher vitality remain unclear. To address this gap, the present study aimed to examine the mediating role of job autonomy in the relationship between humble leadership and teacher vitality, as well as the moderating role of work meaningfulness within the mediation model, based on the conservation of resources theory. A total of 1,202 Chinese primary and secondary school teachers participated in this study. The results showed that humble leadership was significantly and positively associated with both job autonomy and teacher vitality. Teachers’ job autonomy was significantly and positively correlated with their vitality. Furthermore, job autonomy mediated the relationship between humble leadership and teacher vitality. Work meaningfulness not only positively moderated the relationship between humble leadership and teachers’ job autonomy but also moderated the mediating effect of job autonomy in the relationship between humble leadership and teacher vitality. These results emphasized the importance of humble leadership, job autonomy, and work meaningfulness in enhancing teacher vitality.</p>