Some research works have showed that Ghanaian teachers, teaching chemistry in the senior high school, have conceptual difficulties in organic chemistry. This research explored the factors contributing to teacher's conceptual difficulties on teaching organic chemistry to high school students. Through explanatory sequential mixed methods design quantitative data were collected using questionnaire and qualitative data, using semi-structured interviews. The questionnaire was responded to by 71 teachers teaching chemistry in 31 schools, and six teachers, purposively selected, interacted with researchers through interviews to triangulate any quantitative findings. From the quantitative data, four factors, tertiary exposure, professional collaboration, professional competence, and pre-tertiary exposure emerged. These factors were then used as themes to guide the analysis and presentation of results from the qualitative data. To inform further research, it is recommended that chemistry educators and researchers should examine the four factors that predict most of the teacher conceptual difficulties on organic chemistry.