Extraversion and neuroticism influence behaviour and mood. Extreme expressions of these personality traits may predispose individuals to developing chronic functional pains and mood disorders that predominantly affect women. We acquired anatomical MRI scans and personality scores from healthy male and female adolescents and measured gray matter volume (GMV) and cortical thickness to test the hypothesis that neuroticism and extraversion contribute to sex differences in fronto-limbic cortical development during a crucial period of social and biological maturation. In females, extraversion correlated negatively with medial frontal gyrus GMV and neuroticism correlated positively with subgenual anterior cingulate cortex GMV and cortical thickness. Interestingly, correlations between GMV and personality in males showed an opposite effect. Given the association of these cortical areas with social cognition and emotional processing, we suggest that a neuro-maturational divergence during adolescence accounts for the higher prevalence of specific chronic pains and mood disorders in females.