Job exhaustion is not uncommon among Chinese middle school teachers, but the key antecedents of job exhaustion and the underlying mechanisms in this historically underrepresented population remain poorly understood. This study examined the association between job demand and exhaustion, and tested the mediating role of job satisfaction and the moderating role of teachers’ role (i.e., homeroom versus subject) in this association. The two-wave, China Education Panel Survey data from 701 Chinese junior middle school teachers (M = 30.05 years old, SD = 7.86; 78.75% females) were used. Primary hypotheses were tested using structural equation modelling. Results indicated that job load rather than job stress at Wave 1 was positively associated with job exhaustion at Wave 2 indirectly through its negative association with job satisfaction at Wave 2 only among subject teachers; in contrast, for homeroom teachers, job satisfaction at Wave 2 was the only factor that was identified to be negatively associated with job exhaustion at Wave 2. Notably, all significant associations emerged after controlling for a number of covariates, including job exhaustion at Wave 1. Such findings shed initial light on the complexity inherent within the phenomena of middle school teachers’ occupational health in a Chinese cultural context. Reducing teachers’ work load associated with long working hours and promoting teachers’ job satisfaction may be effective ways to relieve and prevent job exhaustion, especially for Chinese subject teachers.