The purpose of this study is to examine the impact of professional development in co-teaching on teacher self-efficacy among general and special education rural high school teachers. A causal-comparative research design was used to survey 256 rural high school teachers from the South and Midwest regions of the U.S. to measure their self-efficacy in student engagement, instructional practices, and classroom management. One-way analysis and independent samples t-test was used to analyze these data using SPSS statistical software. The results indicated a significant difference between teachers with and without experience in a co-teaching classroom regarding their efficacy in using instructional practices. Furthermore, ANOVA results indicated a significant difference in the number of hours of professional development a teacher received in co-teaching as it relates to their efficacy in student engagement, instructional practices, and classroom management. Further discussion and recommendations are also included.