Suicide is a pandemic among global youths and adolescents. Still, there is insufficient evidence to show whether the interactions between bullying victimization, physical inactivity, substance use, and mental health illness aggravate suicidal behaviors among high school students. Based on the Global School-Based Student Health Survey, we analyzed the individual and interaction impacts of bullying victimization, physical inactivity, substance use, and suicidal behaviors among 3,632 adolescents. The 12-month prevalence of suicidal thoughts and plans among senior high school students was over fifty percent. Junior high school students had higher rates of suicide attempts and bullying victimization than senior high school students. Multivariate results indicate that bullying victimization, substance use, and physical inactivity were significantly associated with suicidal thoughts, plans, and attempts among high school students. The interaction of physical inactivity and alcohol was significantly associated with suicidal thoughts in junior high school. In contrast, the interaction of bullying and alcohol was associated with suicidal plans among senior high school adolescents. We hope the findings from this study will generate interventions toward reducing the suicide epidemic in Ghana.