In the USA, African American adolescents aged 13 to 19 years remain disproportionately affected by the negative consequences of sexually risky behaviors. A similar disproportionate impact is experienced by African American adolescents residing in the rural Deep South. Gaming interventions hold promise because they can be designed to be developmentally appropriate and accessible to dispersed populations. We conducted an intervention development qualitative study using focus groups with a total of 129 rural adolescents in three phases. In Phase I, sociocontextual influences on sexual health were explored with 84 participants in two waves of focus groups; to identify critical content for a video gaming intervention. Focus group audio recordings obtained from participants were transcribed verbatim. Transcripts of focus group discussions and observation notes were analyzed using content analysis procedures. The most commonly identified content areas included: making the intervention reflective participants’ daily lives; making sexual health messages implicit not explicit; addressing the role of social media, and tailoring messages to individual players. In Phase 2, using an intervention mapping approach, findings from the first phase were used to develop context specific storylines and essential messages for the video gaming intervention. In phase 3, a different set of 45 participants found the developed game prototype acceptable and relevant. Findings from this study demonstrate the feasibility of partnering with potential users in a multi-phase process of developing a gaming intervention. Healthcare professionals can incorporate gaming principles into educational interventions to enhance engagement populations at risk and patients. More research is needed on the effectiveness of gaming interventions.