A crucial aspect of human development is sexuality which has implications for health, particularly in adolescence, since unfavorable sexual experiences may result in physical and mental problems. Sexuality education interventions (SEI) are one of the most used actions to promote sexual health in adolescents. Nevertheless, there is variability across their components; therefore, key elements for an effective SEI targeted at adolescents (A-SEI) are not well known. Based on this background, this study aims to identify the shared components of successful A-SEI through a systematic review of randomized controlled trials (RCT). This study followed the preferred reporting items for systematic reviews and meta-analyses statement. A search was conducted in CINAHL, PsycInfo, PubMed, and Web of Science between November and December 2021. A total of 21 studies passed the inclusion test after the review of 8318 reports. A total of 18 A-SEIs were identified in these studies. The components analyzed were the intervention’s approach, dose, type of intervention, theoretical framework, facilitators’ training, and intervention methodology. The results established that components that should be present in the design of an effective A-SEI are behavior change theoretical models, the use of participatory methodology, be targeted at mixed-sex groups, facilitators’ training, and at least ten hours of weekly intervention.