In this study, we identified 10 sexuality education programmes from different locations in the USA that aim to give young people knowledge and skills to develop healthy relationships, as well as avoid pregnancy and disease. We conducted in-depth interviews with programme administrators to develop a series of case studies and provide concrete recommendations for education and public health professionals to implement similar approaches in their communities. Many programme administrators succeeded in developing partnerships, adapting existing curricula to suit their environments, engaging external evaluators and garnering support from teachers and parents. However, few programme developers conducted formal needs assessments before developing programmes and many struggled to implement curricula with fidelity and to employ rigorous evaluation designs. Nearly all participants identified concerns over funding as a threat to sustainability. We conclude that schools and organisations need technical assistance to build capacity for rigorous programme planning, implementation and evaluation, as well as additional funding streams to support emerging programmes.