Perinatally HIV-infected (PHIV+) youth are surviving into adolescence and young adulthood. Understanding the sexual development of PHIV+ youth is vital to providing them with developmentally appropriate HIV prevention programs. Using pooled data (N = 417) from two longitudinal studies focused on HIV among youth (51% female; 39% HIV+) and their caregivers (92% female; 46% HIV+), we compared the rate of sexual onset during adolescence across four youth-caregiver combinations: PHIV+ youth with HIV+ caregivers (12%); PHIV+ youth with HIV− caregivers (27%); HIV− youth with HIV+ caregivers (34%); and HIV− youth with HIV-caregivers (27%). Youth with HIV− caregivers were more likely than other youth-caregiver groups to have had their sexual onset. Youth with HIV+ caregivers reported a slower rate of onset of penetrative sex across the adolescent years. We discuss our findings by highlighting the role that both youth and caregiver HIV status play in the onset of sexual behavior across adolescence.