High altitude has always been associated with a higher risk of trauma exposure. However, little is known about the stress-related symptoms and associated factors among trauma-exposed children and adolescents in high plateau areas. This study aimed to investigate the severity of post-traumatic stress symptoms (PTSS) and the associated factors, namely prosocial behavior and resilience, among trauma-exposed children and adolescents in the Qinghai-Tibet Plateau. A cross-sectional study was conducted among 14,428 primary and middle school students and 2,297 trauma-exposed children and adolescents aged 10–19 were included in the final analysis. The PTSS, prosocial behavior, and resilience were measured via three self-reported questionnaires: the Child Post-Traumatic Stress Symptom Scale (CPSS), the Prosocial Behavior Subscale of the Strength and Difficulties Questionnaire (SDQ), and the short version of the Connor-Davidson Resilience Scale (CD-RISC), respectively. A structural equation model was constructed for data analysis. Approximately 70% of trauma-exposed children and adolescents had experienced PTSS, suggesting a probable presence of post-traumatic stress disorder (PTSD). Higher levels of prosocial behavior were significantly associated with fewer PTSS. Furthermore, resilience significantly mediated the relationship between prosocial behavior and PTSS with an indirect effect of − 0.28. The results highlight the severity of PTSS among trauma-exposed youth in high plateau areas. The findings also indicate that prosocial behavior in children and adolescents is a protective factor against the negative outcome of trauma exposure, suggesting that improving prosociality could be an intervention to promote mental health.