Condom utilization at sexual initiation is associated with subsequent condom use and with a decreased risk of sexually transmitted infections (STIs). Our study objective was to determine the factors related to the use of condoms at first sexual intercourse and the level of knowledge about STIs/HIV/AIDS among high school students in grades 11 and 12. A cross-sectional survey was conducted within three secondary schools in Lubumbashi City, D.R. Congo, from 2017. Sampling was exhaustive of the 563 pupils present on the day of the survey. A logistic regression analysis was performed. The mean age of the respondents was 18.2 ± 1.4 years. HIV/AIDS was the most commonly mentioned STI (99.8%). Sexual intercourse was the most quoted path of infection (93.4%) for STIs/HIV/AIDS. Condom use was the most cited form of prevention. Among the respondents, 21.2% had ever been sexually active. The condom was the most commonly used contraceptive (89.1%). The 118 pupils who were sexually active included 13.9% of all girls and 35.3% of all boys with a significant difference (p <0.001). Multivariate analysis showed that children 12 and older, and students who cited their parents as sources of information were more likely to use condoms at first sexual intercourse compared others. Students whose father’s or guardian’s education included university and who reported abstinence as a means to prevent STIs or pregnancy were less likely to use condoms at sexual debut than the others. Hence, family members, leaders and teachers should discuss reproductive health and responsible sexuality earlier with children.