The purpose of this study was to explore the relationships among teachers’ personality traits, work stress, and teaching efficacy. Data were collected on a sample of 341 junior high school teachers in Changhua via survey questionnaires and were analyzed using structural equation modeling. There were a number of findings. First, a model was constructed using teachers’ personality traits, work stress, and teaching efficacy, and the results indicated a reasonable model fit. Second, work stress was found to be a partial mediator between stable emotional traits and teaching efficacy. Teachers’ emotional stability traits negatively predicted work stress and positively predicted teaching efficacy directly, which in turn predicted teaching efficacy indirectly via work stress. Third, work stress was a partial mediator between openness to experience and teaching efficacy. Teachers’ openness to experience directly and positively predicted work stress and teaching efficacy, which in turn predicted teaching efficacy indirectly via work stress. Fourth, work stress was a mediator between agreeableness and teaching efficacy, with full mediating effects. Teachers’ agreeableness positively predicted work stress directly, which in turn predicted teaching efficacy indirectly via work stress. Fifth, teachers’ work stress negatively predicted teaching efficacy. The results of this study could be provided as a reference for educational authorities, teachers and future researchers.