The present study was aimed at investigating the relationships between students' perceived classroom achievement goals, school engagement and substance use in terms of smoking and drinking, and at investigating gender differences regarding these issues in a sample of 1,239 Norwegian 10th grade students. A multivariate analysis showed that motivational and affective school engagement was predicted primarily by the students' perception of a mastery goal structure. However, motivational engagement was significantly more strongly predicted by achievement goal structures among boys than girls, in particular by mastery goal structure. The results also showed that school engagement, particularly motivational engagement, was negatively related to substance use. In conclusion, school engagement seems to be an important multi-dimensional indicator of motivation which is related both to perceived classroom goal structure and to students' substance use in terms of smoking and drinking. Despite the correlational design of the present study, it is reasonable to advise the promotion of a mastery goal structure in the classroom.