Sexually transmitted infections (STIs) pose a significant threat to individual and public health. They disproportionately affect adolescents and young adults. In a cross-sectional study, we assessed self-rated and factual STI knowledge in a sample of 9th graders in 13 secondary schools in Berlin, Germany. Differences by age, gender, migrant background, and school type were quantified using bivariate and multivariable analyses. A total of 1177 students in 61 classes participated. The mean age was 14.6 (SD = 0.7), 47.5% were female, and 52.9% had at least one immigrant parent. Knowledge of human immunodeficiency virus (HIV) was widespread, but other STIs were less known. For example, 46.2% had never heard of chlamydia, 10.8% knew of the HPV vaccination, and only 2.2% were aware that no cure exists for HPV infection. While boys were more likely to describe their knowledge as good, there was no general gender superiority in factual knowledge. Children of immigrants and students in the least academic schools had lower knowledge overall. Our results show that despite their particular risk to contract an STI, adolescents suffer from suboptimal levels of knowledge on STIs beyond HIV. Urgent efforts needed to improve adolescent STI knowledge in order to improve the uptake of primary and secondary prevention.