Adolescent musculoskeletal pain is common and is associated with musculoskeletal pain in adulthood. Psychological symptoms, also common in adolescence, have been shown to be associated with musculoskeletal pain, but the current evidence is mixed and may be dependent on effect modifiers. This study investigated whether adolescents with psychological symptoms (internalizing and externalizing constructs) at age 13 years were at higher odds for musculoskeletal pain at age 17 years and whether the associations were modified by pubertal status and sex. A prospective cohort design examined data on 3865 adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC). Associations between baseline (aged 13 years) internalizing and externalizing symptoms and musculoskeletal pain at follow-up (aged 17 years) were investigated using logistic regression producing odds ratios (OR) and 95% confidence intervals (95% CI). In total 43.1% of adolescents reported musculoskeletal pain at follow-up. Externalizing symptoms at baseline increased the odds of musculoskeletal pain (OR 1.68, 95% CI 1.28, 2.20), and internalizing symptoms demonstrated a non-significant increase (OR 1.26, 95% CI 0.98, 1.62). Effect modification analysis showed an increased effect dependent on pubertal status.Conclusion: Adolescents with externalizing symptoms, and to some extent internalizing symptoms, are at increased odds of later musculoskeletal pain. Future research is now required to understand the reasons for these associations. What is Known: • Current evidence regarding the association between internalizing symptoms and externalizing symptoms and future musculoskeletal pain in adolescents is mixed. What is New: • This study found that adolescents with externalizing symptoms, and to some extent internalizing symptoms, are at increased odds for musculoskeletal pain, with an increased influence dependent on pubertal status. • These results are of interest for the development of timely preventative interventions designed to reduce the risk of musculoskeletal pain.