Differentiated instruction is a proactive teaching model and philosophy with demonstrated potential to cater for diverse learners and create inclusive classrooms. There is little research, however, into the implementation of this approach in the senior secondary classroom. Teachers' implementation of differentiated instruction has been shown to be linked to teacher attitudes and self-efficacy in other settings. This study investigated the impact of teachers' self-efficacy and attitudes towards the implementation of differentiated instruction in the senior secondary context across two Australian states with a total of five participating teachers. The A (Affective) B (Behaviour) C (Cognitive) model was employed to define teacher attitudes from interviews concerning differentiated instruction. Findings indicated that teacher knowledge was a major factor influencing differentiation, in addition to attitude and self-efficacy. The discourse analysis demonstrated that teachers held a greater knowledge of differentiation strategies than the concepts that underpin the differentiated instruction framework. Additionally, time constraints and feelings of failure in implementing differentiation strategies impacted teacher attitudes. Teacher knowledge, attitude and self-efficacy were interrelated and impacted on teachers' implementation of differentiated instruction in the senior secondary classroom. Implications for professional development to address student needs through differentiated instruction in the inclusive senior secondary classroom teacher are discussed.