Although Ghana’s comprehensive sexuality education (CSE) program has been lauded, no study has examined its association with the sexual health outcomes of Ghanaian youth. Using data collected from 2,982 in-school youth (male = 1,820 and female = 1,162) aged 15 to 17 years in three administrative regions of the country, we applied discrete-time hazard models to examine associations between components of Ghana’s CSE on the timing of sexual debut among male and female youth. Results indicate significant relationships between components on HIV prevention and timing of sexual debut for male youth. Male youth who learned about HIV prevention delayed sexual debut; however, male youth who endorsed myths about HIV transmission started sex early. Females who learned about values and interpersonal skills delayed their sexual debut, but the influence of this variable was attenuated by respondents’ demographic characteristics. Female respondents residing in the Greater Accra and Northern regions delayed sex, compared with those in the Brong Ahafo region.