Recent research has shown that internal factors are important predictors of adaptation, but little research has studied the relationship between a sense of coherence and school adaptation. The present study examined the mediating and moderating mechanisms underlying this relationship. A total of 1,072 middle students completed self-report questionnaires assessing their sense of coherence, fathers' and mothers' parenting, empathy, and school adaptation. The results indicated that a sense of coherence was positively associated with school adaptation. A mediation analysis indicated that empathy mediated the relationship between a sense of coherence and school adaptation. Furthermore, both the effect of a sense of coherence on school adaptation and the effect of a sense of coherence on empathy were moderated by positive parenting. The present study contributes to a better understanding of how and when a sense of coherence promotes adolescents' school adaptation.