Objective: The purpose of the current mixed-methods study was to examine self-efficacy and job satisfaction in general education and special education teachers of students with ASD. Method: Using a concurrent mixed methods research design, the quantitative portion of the study examined reports of self-efficacy pertaining to teaching students with ASD and job satisfaction from both general and special education teachers of students with ASD, and examined potential correlates to these constructs such as occupational stress, social support, knowledge of ASD, and school resources. The qualitative portion of the study employed semi-structure interviews to examine what factors influence teachers’ self-efficacy and job satisfaction. Results: Results revealed no significant differences in self-efficacy, job satisfaction, occupational stress, perceived social support or knowledge of ASD between general and special education teachers and no significant relation between self-efficacy and occupational stress, social support and school resources. However, analyses examining the potential relation of these variables with job satisfaction revealed statistically significant correlations between teachers’ job satisfaction and social support and their job satisfaction and levels of occupational stress. The qualitative data for the current study revealed four overarching themes related to overall teacher well-being: the impact of knowledge, experience and training; the importance of support; the impact of occupational stress; and the intrinsic rewards of teaching as protective factors. Following standard mixed methods methodology, quantitative and qualitative data was integrated and discussed.