Developing the confidence to teach is one of the most challenging tasks in the teaching profession. Educators have recognized that the initial years of teaching is complex and challenging. However, no study examines novice teachers' self-efficacy beliefs in teaching multiple subjects in developing countries like Ghana. Novice teachers in Ghana are often deployed to schools and classrooms with high number of students but less number of teachers. Hence, they are faced with teaching multiple subjects per semester (term) aside from the already outlined challenges of novice teachers in literature. The study employed a cross-sectional survey design. Using the Teachers' Sense of Efficacy Scale (TSEBs, long form), novice teachers in Ghana (n = 72) were assessed on how they perceived their efficacy in teaching multiple subjects. Results from the study indicate that novice teachers perceived themselves to be moderately adequate in their TSEBs. Efficacy in classroom management score was lower than in student engagement and instruction strategies. Males also recorded high TSEBs score than females. Majority of the teachers taught large classes (43-53). It is recommended that educators reduce the class size of novice teachers and organize more training and professional development programs for novice teachers.