Many teachers enter classrooms with limited cross-cultural awareness and low levels of confidence to accommodate cultural diversity. Therefore, teaching a heterogeneous body of students requires teachers to have culturally responsive teaching self-efficacy (CRTSE). The investigation of factors impacting teachers’ self-efficacy in teaching diverse students has produced mixed results. The purpose of the current study was to explore the determinants of CRTSE in a sample of Canadian preservice teachers. One hundred and ten preservice teachers from a medium-sized public Canadian University completed measures of political orientation, CRTSE, cross-cultural experiences, and teacher burnout. Higher levels of preservice teachers’ CRTSE were predicted by lower levels of Emotional Exhaustion (i.e., a key aspect of burnout syndrome) and more frequent cross-cultural experiences in their childhood and adolescence. Implications for training preservice teachers are discussed.