We introduce a theoretical framework on teachers’ instructional skills to describe how they can be modeled across different domains. This framework conceptualizes teachers’ instructional skills as action-related skills (during instruction) and reflective skills (before and after instruction), which are considered crucial for coping with the practical demands of everyday teaching in a specific subject. The theoretical framework assumes that both skill facets are influenced by the teacher’s professional knowledge, generic attributes such as general cognitive abilities or ambiguity tolerance as well as affective and motivational factors. To investigate the relationships between teachers’ instructional skills, domain-specific knowledge and generic attributes across different domains, the analytical model focuses on two subjects, mathematics and economics. Based on our study with pre- and in-service teachers of mathematics and economics (N = 564), which for the first time considers two subjects, we present results on these relationships. The findings are discussed with regard to their transferability to other domains.