This article presents a process evaluation of the implementation of the sex education programme the World Starts With Me (WSWM) for secondary school students in Uganda. The purpose of this mixed-methods study was to examine factors associated with dose delivered (number of lessons implemented) and fidelity of implementation (implementation according to the manual), as well as to identify the main barriers and facilitators of implementation. Teachers' confidence in teaching WSWM was negatively associated with dose delivered. Confidence in educating and discussing sexuality issues in class was positively associated with fidelity of implementation, whereas the importance teachers attached to open sex education showed a negative association with fidelity. Main barriers for implementing WSWM were lack of time, unavailability of computers, lack of student manuals and lack of financial support and rewards. Other barriers for successful implementation were related to high turnover of staff and insufficient training and guidance of teachers. Teachers' beliefs/attitudes towards sexuality of adolescents, condom use and sex education were found to be important socio-cognitive factors intervening with full fidelity of implementation. These findings can be used to improve the intervention implementation and to better plan for large-scale dissemination of school-based sex education programmes in sub-Saharan Africa.