Objective: To determine whether biopsychosocial factors are associated with sexual activity and contraceptive utilization among homeless shelter adolescents. Methods: A retrospective study of 440 adolescents at a shelter in Pennsylvania between February 2015 and September 2019 was conducted. The cohort was evaluated to determine what relationship age, gender identity, substance use, and trauma history have with sexual activity and contraceptive utilization. Results: Sexual activity was significantly related to age (mean 15.8+1.4 years in sexually active vs. 14.7+1.6 years in abstinent youth, p<0.001); remote history of self-harm behavior (relative risk ratio (RR) 1.23 [95% CI 1.03-1.46]; p=0.02), history of aggressive behavior (RR 1.21 [95% CI 1.01-1.46]; p=0.04), history of trauma (RR 1.24 [95% CI 1.04-1.48]; p=0.03), and substance use (RR 2.27 [95%CI 1.86-2.77]; p<0.001). There were 55.7% sexually active females vs. 42.50% males reporting contraception use (p=0.01). After adjustment, older age and substance use remained significantly associated with sexual activity (adjusted odds ratio (AOR) 1.58 [95% CI 1.36-1.83]; p<0.001 and AOR 5.18 [95% CI 3.28-8.18]; p<0.001, respectively). Conclusions: Females self-reported sexual activity using contraception more than males. After adjustment, older age and substance use were associated with sexual activity. By better understanding the impact these factors can have on contraceptive utilization, informed policy and practice interventions can be developed and implemented to help increase safe sex practices in spaces where homeless adolescents access healthcare.