Fostering inclusion of students with Special Education Needs (SEN) within mainstream classroom supports positive education outcomes for all. Teachers’ attitudes towards inclusion can also impact; those teachers who perceive themselves as well-trained are more likely to hold positive attitudes towards inclusion. Classroom practices which focus on 21st Century skill development, including collaboration, problem-solving and technology have the potential to positively impact on the education outcomes of students with SEN. The current research sought to explore these themes, and the role a STEM-21st Century Learning by Design (STEM-21CLD) education activity has on teachers’ perceptions and attitudes towards, students with SEN. Nineteen teachers who participated in the STEM-21CLD education activity took part in this qualitative study. Thematic analyses revealed that teachers perceived students differently following participation in the STEM-21CLD activity. Teachers reported seeing students as more confident and capable of leadership. Teachers attitudes towards student with SEN were positively impacted, with a skill focused classroom seen as having a positive influence. Teachers described practical constraints; withdrawal of students for supplementary learning support can mean that these students ‘miss out’ on skill focused learning activities. We argue that the STEM-21CLD learning approach can facilitate teachers to consider inclusive classroom practices in new and innovative ways.