BACKGROUND: Adolescent HIV and pregnancy rates in Southern Africa are amongst the highest in the world. Despite decades of sexual and reproductive health (SRH) programming targeting adolescents, recent trends suggest there is a continued need for interventions targeting condom use for this age group. METHODS: This review synthesises evidence from qualitative studies that describe the determinants of condom use among adolescents in Southern Africa. We conducted systematic searches in four databases. Data were extracted, appraised for quality and analysed using a 'best-fit' framework synthesis approach. RESULTS: We coded deductively findings from 23 original studies using an a priori framework and subsequently conducted thematic analysis. Synthesised findings produced six key themes relating to: 1) pervasive unequal gender norms and restrictive masculinities favouring male sexual decision-making and stigmatising condom use in committed relationships; 2) other social norms reflecting negative constructions of adolescent sexuality and non-traditional family planning; 3) economic and political barriers including poverty and a lack of policy support for condom use; 4) service-level barriers including a lack of youth-friendly SRH services and comprehensive sex education in schools; 5) interpersonal barriers and facilitators including unequal power dynamics in sexual partnerships, peer influences and encouraging condoning condom use, and inadequate communication about SRH from parents/caregivers; and 6) negative attitudes and beliefs about condoms and condom use among adolescents. A conceptual model was generated to describe determinants of condom use, illustrating individual-, interpersonal- and structural-level barriers and facilitating factors. CONCLUSION: SRH programming targeting barriers and facilitators of condom use at multiple levels is recommended in Southern Africa. We present a multilevel integrated model of barriers and facilitators to guide adolescent SRH decision-making, programme planning and evaluation. Given the existence of multilevel barriers and facilitators, interventions should, likewise, take a multilevel approach that incorporates locally relevant understanding of the individual-, interpersonal- and structural-level barriers and facilitators to condom use among adolescents in the region.