Latina/o Americans are at high risk for sexually transmitted infections and adolescent pregnancies. Needed urgently are innovative health promotion approaches that are engaging and culturally sensitive. East Los High is a transmedia edutainment program aimed at young Latina/o Americans. It embeds educational messages in entertainment narratives across digital platforms to promote sexual and reproductive health. We employed online analytics tracking (2013-2014), an online viewer survey (2013), and a laboratory experiment (El Paso, TX, 2014) for season 1 program evaluation. We found that East Los High had a wide audience reach, strong viewer engagement, and a positive cognitive, emotional, and social impact on sexual and reproductive health communication and education. Culturally sensitive transmedia edutainment programs are a promising health promotion strategy for minority populations and warrant further investigation.