The current study examined whether callous-unemotional (CU) traits predicted risky sexual behavior (i.e., unprotected sex, casual sex) and whether substance use and sensation seeking mediated this relationship over 24 months in justice-involved young men. Participants (N = 1,216) were an ethnically and racially diverse sample (46.3% White Latino, 38% Black, 15.7% White non-Latino) of first-time offending male adolescents (ages 13–17 years) from 3 U.S. cities. Participants completed 5 self-reported interviews at 6-month intervals over 2 years. Bootstrapped mediation analyses were conducted to test direct effects of CU traits on risky sexual behaviors, as well as indirect effects through substance use and sensation seeking. CU traits at baseline were positively associated with risky sexual behavior 18–24 months later. CU traits were also associated with the hypothesized mediators, sensation seeking and substance use, measured 6–12 months after baseline. CU traits exerted direct effects on later unprotected sex and casual sex, as well as indirect effects through substance use but not sensation seeking. These effects were largely unchanged when accounting for the youth’s level of self-reported delinquency. These findings demonstrate that CU traits predict later risky sexual outcomes, and this is at least partly explained by substance use. Further, the findings highlight the importance of CU traits for several outcomes that are of significant public health concern among justice-involved adolescents, namely, risky sexual behavior and substance use.