Comprehensive sexuality education (CSE) enables children and young people to learn about the cognitive, emotional, physical, and social characteristics of sexuality. Teachers experience conflicts in teaching CSE due to different cultural and religious backgrounds. This qualitative systematic review aimed to describe the conflicts experienced by teachers in the implementation of CSE in schools. Furthermore, this study aimed to identify the causes of conflict among teachers in implementing CSE. This article focused on teachers’ conflicts in implementing CSE from 2010 to 2022. Online bibliographic databases, such as PubMed, Web of Science, and ERIC, were used to search for relevant articles. A total of 11 studies were included in the review. All 11 studies were conducted in countries with a predominantly Christian population. The majority of the studies were conducted in Africa. The study respondents included teachers, school principals, and school coordinators. The studies identified that CSE implementation is related to multiple conflicts, depending on the context of the country. Five themes on the causes of conflict emerged from the thematic meta-synthesis: (1) Hesitancy in talking about sex education among teachers due to the cultural and religious context; (2) non-integration of traditional sex education into comprehensive sexuality education, (3) fostering effective facilitation of CSE among teachers, (4) determining the appropriate age to start sex education, and (5) roles of stakeholders outside the school. This qualitative systematic review and thematic meta-synthesis highlighted several conflicts among teachers in CSE implementation. Despite the teachers having a perception that sex education should be provided, traditional sex education has not yet transformed to CSE. The study findings also emphasize the need to identify the teacher’s role in CSE implementation. The thematic meta-synthesis also strongly reflected the context of Christianity in Europe and Africa; thus, further research on the religious context in other regions is needed.