Comprehensive Sexuality Education (CSE) is widely recognised as an important educational intervention for promoting sexual and reproductive health, gender equality, and informed decision-making among young people. Despite extensive research on teacher experiences and learner outcomes, limited attention has been given to the perspectives of female school leaders responsible for implementing CSE. This study explored the experiences and perspectives of 15 female school leaders (5 principals, 5 deputy principals, and 5 departmental heads) from the Umlazi and Pinetown districts in KwaZulu-Natal, South Africa. Guided by Transformative Leadership Theory and located within the interpretivist paradigm, the study adopted a qualitative research approach. Data were generated through three focus group discussions and analysed using Braun and Clarke’s thematic analysis framework. The findings revealed four key themes: managing gender and sexual diversity in schools; resistance and acceptance of CSE scripted lesson plans; non-compliance with CSE implementation; and stakeholder involvement and participation. The study found that female school leaders play a crucial role in addressing resistance, fostering stakeholder engagement, and promoting inclusive educational practices. However, effective implementation of CSE continues to be hindered by limited policy understanding, inadequate training, socio-cultural resistance, and inconsistent stakeholder participation. The study recommends enhanced professional development for school leaders and educators, strengthened stakeholder engagement strategies, and improved institutional support mechanisms to facilitate effective CSE implementation. It contributes to the growing scholarship on women in educational leadership by highlighting the role of female leaders in advancing equity, inclusion, and social justice within South African schools.